Evidence Linking Protein Misfolding to Quality Control in Progressive Neurodegenerative Diseases

Author(s): Md. Tanvir Kabir, Md. Sahab Uddin*, Ahmed Abdeen, Ghulam Md Ashraf, Asma Perveen, Abdul Hafeez, May N. Bin-Jumah, Mohamed M. Abdel-Daim

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 23 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Several proteolytic systems including ubiquitin (Ub)-proteasome system (UPS), chaperonemediated autophagy (CMA), and macroautophagy are used by the mammalian cells to remove misfolded proteins (MPs). UPS mediates degradation of most of the MPs, where Ub-conjugated substrates are deubiquitinated, unfolded, and passed through the proteasome’s narrow chamber, and eventually break into smaller peptides. It has been observed that the substrates that show a specific degradation signal, the KFERQ sequence motif, can be delivered to and go through CMA-mediated degradation in lysosomes. Macroautophagy can help in the degradation of substrates that are prone to aggregation and resistant to both the CMA and UPS. In the aforesaid case, cargoes are separated into autophagosomes before lysosomal hydrolase-mediated degradation. Even though the majority of the aggregated and MPs in the human proteome can be removed via cellular protein quality control (PQC), some mutant and native proteins tend to aggregate into β-sheet-rich oligomers that exhibit resistance to all identified proteolytic processes and can, therefore, grow into extracellular plaques or inclusion bodies. Indeed, the buildup of protease-resistant aggregated and MPs is a usual process underlying various protein misfolding disorders, including neurodegenerative diseases (NDs) for example Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. In this article, we have focused on the contribution of PQC in the degradation of pathogenic proteins in NDs.

Keywords: Protein misfolding, Ubiquitin-proteasome system, Macroautophagy, Chaperone mediated autophagy, Neurodegeneration, Amyloid β, Tau.

Sahab Uddin, M.; Ashraf, G.M. Quality Control of Cellular Protein in Neurodegenerative Disorders; IGI Global: Hershey, 2020.
Jones, R.D.; Gardner, R.G. Protein quality control in the nucleus. Curr. Opin. Cell Biol., 2016, 40, 81-89.
[http://dx.doi.org/10.1016/j.ceb.2016.03.002] [PMID: 27015023]
Rao, R.V.; Bredesen, D.E. Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr. Opin. Cell Biol., 2004, 16(6), 653-662.
[http://dx.doi.org/10.1016/j.ceb.2004.09.012] [PMID: 15530777]
Ciechanover, A. Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Bioorg. Med. Chem., 2013, 21(12), 3400-3410.
[http://dx.doi.org/10.1016/j.bmc.2013.01.056] [PMID: 23485445]
Uddin, M.S.; Tewari, D.; Sharma, G.; Kabir, M.T.; Barreto, G.E.; Bin-Jumah, M.N.; Perveen, A.; Abdel-Daim, M.M.; Ashraf, G.M. Molecular mechanisms of ER stress and UPR in the pathogenesis of Alzheimer’s disease. Mol. Neurobiol., 2020, 57, 2902-2919.
[http://dx.doi.org/10.1007/s12035-020-01929-y] [PMID: 32430843]
Al Mamun, A.; Uddin, M.S.; Kabir, M.T.; Khanum, S.; Sarwar, M.S.; Mathew, B.; Rauf, A.; Ahmed, M.; Ashraf, G.M. Exploring the promise of targeting ubiquitin-proteasome system to combat Alzheimer’s disease. Neurotox. Res., 2020, 38(1), 8-17.
[http://dx.doi.org/10.1007/s12640-020-00185-1] [PMID: 32157628]
Sriram, S.M.; Kim, B.Y.; Kwon, Y.T. The N-end rule pathway: emerging functions and molecular principles of substrate recognition. Nat. Rev. Mol. Cell Biol., 2011, 12(11), 735-747.
[http://dx.doi.org/10.1038/nrm3217] [PMID: 22016057]
Tasaki, T.; Sriram, S.M.; Park, K.S.; Kwon, Y.T. The N-end rule pathway. Annu. Rev. Biochem., 2012, 81, 261-289.
[http://dx.doi.org/10.1146/annurev-biochem-051710-093308] [PMID: 22524314]
Kim, S.T.; Tasaki, T.; Zakrzewska, A.; Yoo, Y.D.; Sa Sung, K.; Kim, S-H.; Cha-Molstad, H.; Hwang, J.; Kim, K.A.; Kim, B.Y.; Kwon, Y.T. The N-end rule proteolytic system in autophagy. Autophagy, 2013, 9(7), 1100-1103.
[http://dx.doi.org/10.4161/auto.24643] [PMID: 23628846]
Rahman, M.A.; Saha, S.K.; Rahman, M.S.; Uddin, M.J.; Uddin, M.S.; Pang, M-G.; Rhim, H.; Cho, S-G. Molecular insights into therapeutic potential of autophagy modulation by natural products for cancer stem cells. Front. Cell Dev. Biol., 2020, 8, 283.
[http://dx.doi.org/10.3389/fcell.2020.00283] [PMID: 32391363]
Rothenberg, C.; Srinivasan, D.; Mah, L.; Kaushik, S.; Peterhoff, C.M.; Ugolino, J.; Fang, S.; Cuervo, A.M.; Nixon, R.A.; Monteiro, M.J. Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Hum. Mol. Genet., 2010, 19(16), 3219-3232.
[http://dx.doi.org/10.1093/hmg/ddq231] [PMID: 20529957]
Kiffin, R.; Christian, C.; Knecht, E.; Cuervo, A.M. Activation of chaperone-mediated autophagy during oxidative stress. Mol. Biol. Cell, 2004, 15(11), 4829-4840.
[http://dx.doi.org/10.1091/mbc.e04-06-0477] [PMID: 15331765]
Hariharan, N.; Zhai, P.; Sadoshima, J. Oxidative stress stimulates autophagic flux during ischemia/reperfusion. Antioxid. Redox Signal., 2011, 14(11), 2179-2190.
[http://dx.doi.org/10.1089/ars.2010.3488] [PMID: 20812860]
Koga, H.; Cuervo, A.M. Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. Neurobiol. Dis., 2011, 43(1), 29-37.
[http://dx.doi.org/10.1016/j.nbd.2010.07.006] [PMID: 20643207]
Uddin, M.S.; Kabir, M.T.; Rahman, M.M.; Mathew, B.; Shah, M.A.; Ashraf, G.M. TV 3326 for Alzheimer’s dementia: a novel multimodal CHE and MAO inhibitors to mitigate Alzheimer’s‐like neuropathology. J. Pharm. Pharmacol., 2020, 72(8), 1001-1012.
Kabir, M.T.; Uddin, M.S.; Mamun, A.A.; Jeandet, P.; Aleya, L.; Mansouri, R.A.; Ashraf, G.M.; Mathew, B.; Bin-Jumah, M.N.; Abdel-Daim, M.M. Combination drug therapy for the management of Alzheimer’s disease. Int. J. Mol. Sci., 2020, 21(9), 3272.
[http://dx.doi.org/10.3390/ijms21093272] [PMID: 32380758]
Uddin, M.S.; Tewari, D.; Mamun, A.A.; Kabir, M.T.; Niaz, K.; Wahed, M.I.I.; Barreto, G.E.; Ashraf, G.M. Circadian and sleep dysfunction in Alzheimer’s disease. Ageing Res. Rev., 2020, 60, 101046.
[http://dx.doi.org/10.1016/j.arr.2020.101046] [PMID: 32171783]
Uddin, M.S.; Kabir, M.T.; Mamun, A.A.; Barreto, G.E.; Rashid, M.; Perveen, A.; Ashraf, G.M. Pharmacological approaches to mitigate neuroinflammation in Alzheimer’s disease. Int. Immunopharmacol., 2020, 84, 106479.
[http://dx.doi.org/10.1016/j.intimp.2020.106479] [PMID: 32353686]
Kopito, R.R. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol., 2000, 10(12), 524-530.
[http://dx.doi.org/10.1016/S0962-8924(00)01852-3] [PMID: 11121744]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science, 2002, 297, 353-359.
Ward, S.M.; Himmelstein, D.S.; Lancia, J.K.; Binder, L.I. Tau oligomers and tau toxicity in neurodegenerative disease. Biochem. Soc. Trans., 2012, 40(4), 667-671.
[http://dx.doi.org/10.1042/BST20120134] [PMID: 22817713]
Uddin, M.S.; Al Mamun, A.; Rahman, M.A.; Behl, T.; Perveen, A.; Hafeez, A.; Bin-Jumah, M.N.; Abdel-Daim, M.M.; Ashraf, G.M. Emerging proof of protein misfolding and interactions in multifactorial Alzheimer’s disease. Curr. Top. Med. Chem., 2020, 20.
[http://dx.doi.org/10.2174/1568026620666200601161703 ] [PMID: 32479244]
Griffith, J.S. Self-replication and scrapie. Nature, 1967, 215(5105), 1043-1044.
[http://dx.doi.org/10.1038/2151043a0] [PMID: 4964084]
Prusiner, S. Novel proteinaceous infectious particles cause scrapie. Science, 1982, 216, 136-144.
Prusiner, S.B. Prions. Proc. Natl. Acad. Sci. USA, 1998, 95(23), 13363-13383.
[http://dx.doi.org/10.1073/pnas.95.23.13363] [PMID: 9811807]
Andersen, P.M.; Al-Chalabi, A. Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat. Rev. Neurol., 2011, 7(11), 603-615.
[http://dx.doi.org/10.1038/nrneurol.2011.150] [PMID: 21989245]
Martin, I.; Dawson, V.L.; Dawson, T.M. Recent advances in the genetics of Parkinson’s disease. Annu. Rev. Genomics Hum. Genet., 2011, 12, 301-325.
[http://dx.doi.org/10.1146/annurev-genom-082410-101440] [PMID: 21639795]
Uversky, V.N. Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J. Neurochem., 2007, 103(1), 17-37.
[PMID: 17623039]
Williams, A.; Sarkar, S.; Cuddon, P.; Ttofi, E.K.; Saiki, S.; Siddiqi, F.H.; Jahreiss, L.; Fleming, A.; Pask, D.; Goldsmith, P.; O’Kane, C.J.; Floto, R.A.; Rubinsztein, D.C. Novel targets for Huntington’s disease in an mTOR-independent autophagy pathway. Nat. Chem. Biol., 2008, 4(5), 295-305.
[http://dx.doi.org/10.1038/nchembio.79] [PMID: 18391949]
Tsoi, H.; Lau, T.C-K.; Tsang, S-Y.; Lau, K-F.; Chan, H.Y.E. CAG expansion induces nucleolar stress in polyglutamine diseases. Proc. Natl. Acad. Sci. USA, 2012, 109(33), 13428-13433.
[http://dx.doi.org/10.1073/pnas.1204089109] [PMID: 22847428]
Demuro, A.; Mina, E.; Kayed, R.; Milton, S.C.; Parker, I.; Glabe, C.G. Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers. J. Biol. Chem., 2005, 280(17), 17294-17300.
[http://dx.doi.org/10.1074/jbc.M500997200] [PMID: 15722360]
Lee, S.; Sato, Y.; Nixon, R.A. Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer’s-like axonal dystrophy. J. Neurosci., 2011, 31(21), 7817-7830.
[http://dx.doi.org/10.1523/JNEUROSCI.6412-10.2011] [PMID: 21613495]
Hollenbeck, P.J. Products of endocytosis and autophagy are retrieved from axons by regulated retrograde organelle transport. J. Cell Biol., 1993, 121(2), 305-315.
[http://dx.doi.org/10.1083/jcb.121.2.305] [PMID: 7682217]
Larsen, K.E.; Sulzer, D. Autophagy in neurons: a review. Histol. Histopathol., 2002, 17(3), 897-908.
[PMID: 12168801]
Hara, T.; Nakamura, K.; Matsui, M.; Yamamoto, A.; Nakahara, Y.; Suzuki-Migishima, R.; Yokoyama, M.; Mishima, K.; Saito, I.; Okano, H.; Mizushima, N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature, 2006, 441(7095), 885-889.
[http://dx.doi.org/10.1038/nature04724] [PMID: 16625204]
Mizushima, N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr. Opin. Cell Biol., 2010, 22(2), 132-139.
[http://dx.doi.org/10.1016/j.ceb.2009.12.004] [PMID: 20056399]
Keller, J.N.; Huang, F.F.; Markesbery, W.R. Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience, 2000, 98(1), 149-156.
[http://dx.doi.org/10.1016/S0306-4522(00)00067-1] [PMID: 10858621]
Jung, K-M.; Astarita, G.; Zhu, C.; Wallace, M.; Mackie, K.; Piomelli, D. A key role for diacylglycerol lipase-α in metabotropic glutamate receptor-dependent endocannabinoid mobilization. Mol. Pharmacol., 2007, 72(3), 612-621.
[http://dx.doi.org/10.1124/mol.107.037796] [PMID: 17584991]
Tydlacka, S.; Wang, C-E.; Wang, X.; Li, S.; Li, X-J. Differential activities of the ubiquitin-proteasome system in neurons versus glia may account for the preferential accumulation of misfolded proteins in neurons. J. Neurosci., 2008, 28(49), 13285-13295.
[http://dx.doi.org/10.1523/JNEUROSCI.4393-08.2008] [PMID: 19052220]
Dantuma, N.P.; Lindsten, K. Stressing the ubiquitin-proteasome system. Cardiovasc. Res., 2010, 85(2), 263-271.
[http://dx.doi.org/10.1093/cvr/cvp255] [PMID: 19633314]
Löw, K.; Aebischer, P. Use of viral vectors to create animal models for Parkinson’s disease. Neurobiol. Dis., 2012, 48(2), 189-201.
[http://dx.doi.org/10.1016/j.nbd.2011.12.038] [PMID: 22227451]
Tai, H-C.; Serrano-Pozo, A.; Hashimoto, T.; Frosch, M.P.; Spires-Jones, T.L.; Hyman, B.T. The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system. Am. J. Pathol., 2012, 181(4), 1426-1435.
[http://dx.doi.org/10.1016/j.ajpath.2012.06.033] [PMID: 22867711]
Webb, J.L.; Ravikumar, B.; Atkins, J.; Skepper, J.N.; Rubinsztein, D.C. α-Synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem., 2003, 278(27), 25009-25013.
[http://dx.doi.org/10.1074/jbc.M300227200] [PMID: 12719433]
Sarkar, S.; Krishna, G.; Imarisio, S.; Saiki, S.; O’Kane, C.J.; Rubinsztein, D.C. A rational mechanism for combination treatment of Huntington’s disease using lithium and rapamycin. Hum. Mol. Genet., 2008, 17(2), 170-178.
[http://dx.doi.org/10.1093/hmg/ddm294] [PMID: 17921520]
Heiseke, A.; Aguib, Y.; Riemer, C.; Baier, M.; Schätzl, H.M. Lithium induces clearance of protease resistant prion protein in prion-infected cells by induction of autophagy. J. Neurochem., 2009, 109(1), 25-34.
[http://dx.doi.org/10.1111/j.1471-4159.2009.05906.x] [PMID: 19183256]
Caccamo, A.; Majumder, S.; Richardson, A.; Strong, R.; Oddo, S. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J. Biol. Chem., 2010, 285(17), 13107-13120.
[http://dx.doi.org/10.1074/jbc.M110.100420] [PMID: 20178983]
Rodriguez-Navarro, J.A.; Cuervo, A.M. Autophagy and lipids: tightening the knot. Semin. Immunopathol., 2010, 32(4), 343-353.
[http://dx.doi.org/10.1007/s00281-010-0219-7] [PMID: 20730586]
Spilman, P.; Podlutskaya, N.; Hart, M.J.; Debnath, J.; Gorostiza, O.; Bredesen, D.; Richardson, A.; Strong, R.; Galvan, V. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-β levels in a mouse model of Alzheimer’s disease. PLoS One, 2010, 5(4), e9979.
[http://dx.doi.org/10.1371/journal.pone.0009979] [PMID: 20376313]
Hershko, A.; Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem., 1998, 67, 425-479.
[http://dx.doi.org/10.1146/annurev.biochem.67.1.425] [PMID: 9759494]
Qian, S.B.; McDonough, H.; Boellmann, F.; Cyr, D.M.; Patterson, C. CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature, 2006, 440(7083), 551-555.
[http://dx.doi.org/10.1038/nature04600] [PMID: 16554822]
Upadhya, S.C.; Hegde, A.N. Role of the ubiquitin proteasome system in Alzheimer’s disease. BMC Biochem., 2007, 8(Suppl. 1), S12.
[http://dx.doi.org/10.1186/1471-2091-8-S1-S12] [PMID: 18047736]
Peng, J.; Schwartz, D.; Elias, J.E.; Thoreen, C.C.; Cheng, D.; Marsischky, G.; Roelofs, J.; Finley, D.; Gygi, S.P. A proteomics approach to understanding protein ubiquitination. Nat. Biotechnol., 2003, 21(8), 921-926.
[http://dx.doi.org/10.1038/nbt849] [PMID: 12872131]
Hadian, K.; Griesbach, R.A.; Dornauer, S.; Wanger, T.M.; Nagel, D.; Metlitzky, M.; Beisker, W.; Schmidt-Supprian, M.; Krappmann, D. NF-κB essential modulator (NEMO) interaction with linear and lys-63 ubiquitin chains contributes to NF-κB activation. J. Biol. Chem., 2011, 286(29), 26107-26117.
[http://dx.doi.org/10.1074/jbc.M111.233163] [PMID: 21622571]
Matsumoto, M.L.; Wickliffe, K.E.; Dong, K.C.; Yu, C.; Bosanac, I.; Bustos, D.; Phu, L.; Kirkpatrick, D.S.; Hymowitz, S.G.; Rape, M.; Kelley, R.F.; Dixit, V.M. K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody. Mol. Cell, 2010, 39(3), 477-484.
[http://dx.doi.org/10.1016/j.molcel.2010.07.001] [PMID: 20655260]
Morawe, T.; Hiebel, C.; Kern, A.; Behl, C. Protein homeostasis, aging and Alzheimer’s disease. Mol. Neurobiol., 2012, 46(1), 41-54.
[http://dx.doi.org/10.1007/s12035-012-8246-0] [PMID: 22361852]
Ravikumar, B.; Sarkar, S.; Rubinsztein, D.C. Clearance of mutant aggregate-prone proteins by autophagy. Methods Mol. Biol., 2008, 445, 195-211.
[http://dx.doi.org/10.1007/978-1-59745-157-4_13] [PMID: 18425452]
Douglas, P.M.; Summers, D.W.; Cyr, D.M. Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways. Prion, 2009, 3(2), 51-58.
[http://dx.doi.org/10.4161/pri.3.2.8587] [PMID: 19421006]
Cha-Molstad, H.; Sung, K.S.; Hwang, J.; Kim, K.A.; Yu, J.E.; Yoo, Y.D.; Jang, J.M.; Han, D.H.; Molstad, M.; Kim, J.G.; Lee, Y.J.; Zakrzewska, A.; Kim, S.H.; Kim, S.T.; Kim, S.Y.; Lee, H.G.; Soung, N.K.; Ahn, J.S.; Ciechanover, A.; Kim, B.Y.; Kwon, Y.T. Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding. Nat. Cell Biol., 2015, 17(7), 917-929.
[http://dx.doi.org/10.1038/ncb3177] [PMID: 26075355]
Kloetzel, P.M.; Ossendorp, F. Proteasome and peptidase function in MHC-class-I-mediated antigen presentation. Curr. Opin. Immunol., 2004, 16(1), 76-81.
[http://dx.doi.org/10.1016/j.coi.2003.11.004] [PMID: 14734113]
Gardner, R.G.; Nelson, Z.W.; Gottschling, D.E. Degradation-mediated protein quality control in the nucleus. Cell, 2005, 120(6), 803-815.
[http://dx.doi.org/10.1016/j.cell.2005.01.016] [PMID: 15797381]
Heck, J.W.; Cheung, S.K.; Hampton, R.Y. Cytoplasmic protein quality control degradation mediated by parallel actions of the E3 ubiquitin ligases Ubr1 and San1. Proc. Natl. Acad. Sci. USA, 2010, 107(3), 1106-1111.
[http://dx.doi.org/10.1073/pnas.0910591107] [PMID: 20080635]
Kettern, N.; Dreiseidler, M.; Tawo, R.; Höhfeld, J. Chaperone-assisted degradation: multiple paths to destruction. Biol. Chem., 2010, 391(5), 481-489.
[http://dx.doi.org/10.1515/bc.2010.058] [PMID: 20302520]
Fang, N.N.; Ng, A.H.M.; Measday, V.; Mayor, T. Hul5 HECT ubiquitin ligase plays a major role in the ubiquitylation and turnover of cytosolic misfolded proteins. Nat. Cell Biol., 2011, 13(11), 1344-1352.
[http://dx.doi.org/10.1038/ncb2343] [PMID: 21983566]
Rodrigo-Brenni, M.C.; Gutierrez, E.; Hegde, R.S. Cytosolic quality control of mislocalized proteins requires RNF126 recruitment to Bag6. Mol. Cell, 2014, 55(2), 227-237.
[http://dx.doi.org/10.1016/j.molcel.2014.05.025] [PMID: 24981174]
Bengtson, M.H.; Joazeiro, C.A. Role of a ribosome-associated E3 ubiquitin ligase in protein quality control. Nature, 2010, 467(7314), 470-473.
[http://dx.doi.org/10.1038/nature09371] [PMID: 20835226]
Nielsen, S.V.; Poulsen, E.G.; Rebula, C.A.; Hartmann-Petersen, R. Protein quality control in the nucleus. Biomolecules, 2014, 4(3), 646-661.
[http://dx.doi.org/10.3390/biom4030646] [PMID: 25010148]
Vembar, S.S.; Brodsky, J.L. One step at a time: endoplasmic reticulum-associated degradation. Nat. Rev. Mol. Cell Biol., 2008, 9(12), 944-957.
[http://dx.doi.org/10.1038/nrm2546] [PMID: 19002207]
Hao, R.; Nanduri, P.; Rao, Y.; Panichelli, R.S.; Ito, A.; Yoshida, M.; Yao, T.P. Proteasomes activate aggresome disassembly and clearance by producing unanchored ubiquitin chains. Mol. Cell, 2013, 51(6), 819-828.
[http://dx.doi.org/10.1016/j.molcel.2013.08.016] [PMID: 24035499]
Crosas, B.; Hanna, J.; Kirkpatrick, D.S.; Zhang, D.P.; Tone, Y.; Hathaway, N.A.A.; Buecker, C.; Leggett, D.S.; Schmidt, M.; King, R.W.; Gygi, S.P.P.; Finley, D. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell, 2006, 127(7), 1401-1413.
[http://dx.doi.org/10.1016/j.cell.2006.09.051] [PMID: 17190603]
Lee, B-H.; Lee, M.J.; Park, S.; Oh, D-C.; Elsasser, S.; Chen, P-C.; Gartner, C.; Dimova, N.; Hanna, J.; Gygi, S.P.; Wilson, S.M.; King, R.W.; Finley, D. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature, 2010, 467(7312), 179-184.
[http://dx.doi.org/10.1038/nature09299] [PMID: 20829789]
Chiang, H.L.; Terlecky, S.R.; Plant, C.P.; Dice, J.F. A role for a 70-kilodaton heat shock protein in lysosomal degradation of intracellular proteins. Science, 1989, 246, 382-385.
Dice, J.F. Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends Biochem. Sci., 1990, 15(8), 305-309.
[http://dx.doi.org/10.1016/0968-0004(90)90019-8] [PMID: 2204156]
Cuervo, A.M.; Dice, J.F.; Knecht, E. A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J. Biol. Chem., 1997, 272(9), 5606-5615.
[http://dx.doi.org/10.1074/jbc.272.9.5606] [PMID: 9038169]
Fuertes, G.; Martín De Llano, J.J.; Villarroya, A.; Rivett, A.J.; Knecht, E. Changes in the proteolytic activities of proteasomes and lysosomes in human fibroblasts produced by serum withdrawal, amino-acid deprivation and confluent conditions. Biochem. J., 2003, 375(Pt 1), 75-86.
[http://dx.doi.org/10.1042/bj20030282] [PMID: 12841850]
Massey, A.C.; Kaushik, S.; Sovak, G.; Kiffin, R.; Cuervo, A.M. Consequences of the selective blockage of chaperone-mediated autophagy. Proc. Natl. Acad. Sci. USA, 2006, 103(15), 5805-5810.
[http://dx.doi.org/10.1073/pnas.0507436103] [PMID: 16585521]
Kaushik, S.; Cuervo, A.M. Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol., 2012, 22(8), 407-417.
[http://dx.doi.org/10.1016/j.tcb.2012.05.006] [PMID: 22748206]
Chiang, H.L.; Dice, J.F. Peptide sequences that target proteins for enhanced degradation during serum withdrawal. J. Biol. Chem., 1988, 263(14), 6797-6805.
[PMID: 3360807]
Agarraberes, F.A.; Dice, J.F. A molecular chaperone complex at the lysosomal membrane is required for protein translocation. J. Cell Sci., 2001, 114(Pt 13), 2491-2499.
[PMID: 11559757]
Cuervo, A.M.; Dice, J.F. A receptor for the selective uptake and degradation of proteins by lysosomes. Science, 1996, 273, 501-503 1996, 273, 501-503., 1996.
Bandyopadhyay, U.; Kaushik, S.; Varticovski, L.; Cuervo, A.M. The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Mol. Cell. Biol., 2008, 28(18), 5747-5763.
[http://dx.doi.org/10.1128/MCB.02070-07] [PMID: 18644871]
Cuervo, A.M.; Knecht, E.; Terlecky, S.R.; Dice, J.F. Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation. Am. J. Physiol., 1995, 269(5 Pt 1), C1200-C1208.
[http://dx.doi.org/10.1152/ajpcell.1995.269.5.C1200] [PMID: 7491910]
Agarraberes, F.A.; Terlecky, S.R.; Dice, J.F. An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J. Cell Biol., 1997, 137(4), 825-834.
[http://dx.doi.org/10.1083/jcb.137.4.825] [PMID: 9151685]
Cuervo, A.M.; Dice, J.F. Regulation of lamp2a levels in the lysosomal membrane. Traffic, 2000, 1(7), 570-583.
[http://dx.doi.org/10.1034/j.1600-0854.2000.010707.x] [PMID: 11208145]
Wing, S.S.; Chiang, H.L.; Goldberg, A.L.; Dice, J.F. Proteins containing peptide sequences related to Lys-Phe-Glu-Arg-Gln are selectively depleted in liver and heart, but not skeletal muscle, of fasted rats. Biochem. J., 1991, 275(Pt 1), 165-169.
[http://dx.doi.org/10.1042/bj2750165] [PMID: 2018472]
Cuervo, A.M.; Stafanis, L.; Fredenburg, R.; Lansbury, P.T.; Sulzer, D. D. Impaired degradation of mutant α-synuclein by chaperonemediated autophagy Science (80-. ) 2004, 2004, 1292-1295.
Lamark, T.; Kirkin, V.; Dikic, I.; Johansen, T. NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets. Cell Cycle, 2009, 8(13), 1986-1990.
[http://dx.doi.org/10.4161/cc.8.13.8892] [PMID: 19502794]
Stolz, A.; Ernst, A.; Dikic, I. Cargo recognition and trafficking in selective autophagy. Nat. Cell Biol., 2014, 16(6), 495-501.
[http://dx.doi.org/10.1038/ncb2979] [PMID: 24875736]
Uddin, M.S.; Kabir, M.T.; Tewari, D.; Mathew, B.; Aleya, L. Emerging signal regulating potential of small molecule biflavonoids to combat neuropathological insults of Alzheimer’s disease. Sci. Total Environ., 2020, 700, 134836.
[http://dx.doi.org/10.1016/j.scitotenv.2019.134836] [PMID: 31704512]
Al Mamun, A.; Uddin, M.S. KDS2010: A potent highly selective and reversible MAO-B inhibitor to abate Alzheimer’s disease. Comb. Chem. High Throughput Screen, 2020, ePub ahead of print
[http://dx.doi.org/10.2174/1386207323666200117103144] [PMID: 31957612]
Uddin, M.S.; Kabir, M.T.; Tewari, D.; Al Mamun, A.; Mathew, B.; Aleya, L.; Barreto, G.E.; Bin-Jumah, M.N.; Abdel-Daim, M.M.; Ashraf, G.M. Revisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer’s disease. J. Neurol. Sci., 2020, 416, 116974.
[http://dx.doi.org/10.1016/j.jns.2020.116974 ] [PMID: 32559516]
Uddin, M.S.; Mamun, A.A.; Takeda, S.; Sarwar, M.S.; Begum, M.M. Analyzing the chance of developing dementia among geriatric people: a cross-sectional pilot study in Bangladesh. Psychogeriatrics, 2019, 19(2), 87-94.
[http://dx.doi.org/10.1111/psyg.12368] [PMID: 30221441]
Kabir, M.T.; Uddin, M.S.; Mathew, B.; Das, P.K.; Ashraf, G.M.; Ashraf, G.M. Emerging promise of immunotherapy for Alzheimer’s disease: a new hope for the development of Alzheimer’s vaccine. Curr. Top. Med. Chem., 2020, 20, 1214-1234.
[http://dx.doi.org/10.2174/1568026620666200422105156] [PMID: 32321405]
Al Mamun, A.; Uddin, M.S.; Bin Bashar, M.F.; Zaman, S.; Begum, Y.; Bulbul, I.J.; Islam, M.S.; Sarwar, M.S.; Mathew, B.; Amran, M.S.; Md Ashraf, G.; Bin-Jumah, M.N.; Mousa, S.A.; Abdel-Daim, M.M. Molecular insight into the therapeutic promise of targeting APOE4 for Alzheimer’s disease. Oxid. Med. Cell. Longev., 2020, 2020, 5086250.
Hossain, M.F.; Uddin, M.S.; Uddin, G.M.S.; Sumsuzzman, D.M.; Islam, M.S.; Barreto, G.E.; Mathew, B.; Ashraf, G.M. Melatonin in Alzheimer’s disease: a latent endogenous regulator of neurogenesis to mitigate Alzheimer’s neuropathology. Mol. Neurobiol., 2019, 56(12), 8255-8276.
[http://dx.doi.org/10.1007/s12035-019-01660-3] [PMID: 31209782]
Kabir, M.T.; Uddin, M.S.; Begum, M.M.; Thangapandiyan, S.; Rahman, M.S.; Aleya, L.; Mathew, B.; Ahmed, M.; Barreto, G.E.; Ashraf, G.M. Cholinesterase inhibitors for Alzheimer’s disease: multitargeting strategy based on anti-Alzheimer’s drugs repositioning. Curr. Pharm. Des., 2019, 25(33), 3519-3535.
[http://dx.doi.org/10.2174/1381612825666191008103141] [PMID: 31593530]
Uddin, M.S.; Rahman, M.M.; Jakaria, M.; Rahman, M.S.; Hossain, M.S.; Islam, A.; Ahmed, M.; Mathew, B.; Omar, U.M.; Barreto, G.E.; Ashraf, G.M. Estrogen signaling in Alzheimer’s disease: molecular insights and therapeutic targets for Alzheimer’s dementia. Mol. Neurobiol., 2020, 57(6), 2654-2670.
[http://dx.doi.org/10.1007/s12035-020-01911-8] [PMID: 32297302]
Uddin, M.S.; Kabir, M.T. Emerging signal regulating potential of genistein against Alzheimer’s disease: a promising molecule of interest. Front. Cell Dev. Biol., 2019, 7, 197.
[http://dx.doi.org/10.3389/fcell.2019.00197] [PMID: 31620438]
Zaplatic, E.; Bule, M.; Shah, S.Z.A.; Uddin, M.S.; Niaz, K. Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer’s disease. Life Sci., 2019, 224, 109-119.
[http://dx.doi.org/10.1016/j.lfs.2019.03.055] [PMID: 30914316]
Uddin, M.S.; Kabir, M.T.; Jeandet, P.; Mathew, B.; Ashraf, G.M.; Perveen, A.; Bin-Jumah, M.N.; Mousa, S.A.; Abdel-Daim, M.M. Novel anti-Alzheimer’s therapeutic molecules targeting amyloid precursor protein processing. Oxid. Med. Cell. Longev., 2020, 2020, 7039138.
[http://dx.doi.org/10.1155/2020/7039138] [PMID: 32411333]
De Strooper, B. Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron, 2003, 38(1), 9-12.
[http://dx.doi.org/10.1016/S0896-6273(03)00205-8] [PMID: 12691659]
Kumar, P.; Ambasta, R.K.; Veereshwarayya, V.; Rosen, K.M.; Kosik, K.S.; Band, H.; Mestril, R.; Patterson, C.; Querfurth, H.W. CHIP and HSPs interact with β-APP in a proteasome-dependent manner and influence Abeta metabolism. Hum. Mol. Genet., 2007, 16(7), 848-864.
[http://dx.doi.org/10.1093/hmg/ddm030] [PMID: 17317785]
Atkin, G.; Hunt, J.; Minakawa, E.; Sharkey, L.; Tipper, N.; Tennant, W.; Paulson, H.L. F-box only protein 2 (Fbxo2) regulates amyloid precursor protein levels and processing. J. Biol. Chem., 2014, 289(10), 7038-7048.
[http://dx.doi.org/10.1074/jbc.M113.515056] [PMID: 24469452]
Kaneko, M.; Koike, H.; Saito, R.; Kitamura, Y.; Okuma, Y.; Nomura, Y. Loss of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and amyloid-beta generation. J. Neurosci., 2010, 30(11), 3924-3932.
[http://dx.doi.org/10.1523/JNEUROSCI.2422-09.2010] [PMID: 20237263]
El Ayadi, A.; Stieren, E.S.; Barral, J.M.; Boehning, D. Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of lysine 688. Proc. Natl. Acad. Sci. USA, 2012, 109(33), 13416-13421.
[http://dx.doi.org/10.1073/pnas.1206786109] [PMID: 22847417]
Thinakaran, G.; Koo, E.H. Amyloid precursor protein trafficking, processing, and function. J. Biol. Chem., 2008, 283(44), 29615-29619.
[http://dx.doi.org/10.1074/jbc.R800019200] [PMID: 18650430]
Perry, G.; Friedman, R.; Shaw, G.; Chau, V. Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc. Natl. Acad. Sci. USA, 1987, 84(9), 3033-3036.
[http://dx.doi.org/10.1073/pnas.84.9.3033] [PMID: 3033674]
Pickford, F.; Masliah, E.; Britschgi, M.; Lucin, K.; Narasimhan, R.; Jaeger, P.A.; Small, S.; Spencer, B.; Rockenstein, E.; Levine, B.; Wyss-Coray, T. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J. Clin. Invest., 2008, 118(6), 2190-2199.
[http://dx.doi.org/10.1172/JCI33585] [PMID: 18497889]
Komatsu, M.; Waguri, S.; Chiba, T.; Murata, S.; Iwata, J.; Tanida, I.; Ueno, T.; Koike, M.; Uchiyama, Y.; Kominami, E.; Tanaka, K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature, 2006, 441(7095), 880-884.
[http://dx.doi.org/10.1038/nature04723] [PMID: 16625205]
Liang, C-C.; Wang, C.; Peng, X.; Gan, B.; Guan, J-L. Neural-specific deletion of FIP200 leads to cerebellar degeneration caused by increased neuronal death and axon degeneration. J. Biol. Chem., 2010, 285(5), 3499-3509.
[http://dx.doi.org/10.1074/jbc.M109.072389] [PMID: 19940130]
Uddin, M.S.; Stachowiak, A.; Mamun, A.A.; Tzvetkov, N.T.; Takeda, S.; Atanasov, A.G.; Bergantin, L.B.; Abdel-Daim, M.M.; Stankiewicz, A.M. Autophagy and Alzheimer’s disease: from molecular mechanisms to therapeutic implications. Front. Aging Neurosci., 2018, 10, 04
[http://dx.doi.org/10.3389/fnagi.2018.00004] [PMID: 29441009]
Uddin, M.S.; Mamun, A.A.; Labu, Z.K.; Hidalgo-Lanussa, O.; Barreto, G.E.; Ashraf, G.M. Autophagic dysfunction in Alzheimer’s disease: cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis. J. Cell. Physiol., 2019, 234(6), 8094-8112.
[http://dx.doi.org/10.1002/jcp.27588] [PMID: 30362531]
Nixon, R.A.; Wegiel, J.; Kumar, A.; Yu, W.H.; Peterhoff, C.; Cataldo, A.; Cuervo, A.M. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J. Neuropathol. Exp. Neurol., 2005, 64(2), 113-122.
[http://dx.doi.org/10.1093/jnen/64.2.113] [PMID: 15751225]
Boland, B.; Kumar, A.; Lee, S.; Platt, F.M.; Wegiel, J.; Yu, W.H.; Nixon, R.A. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J. Neurosci., 2008, 28(27), 6926-6937.
[http://dx.doi.org/10.1523/JNEUROSCI.0800-08.2008] [PMID: 18596167]
Nixon, R.A.; Yang, D-S. Autophagy failure in Alzheimer’s disease--locating the primary defect. Neurobiol. Dis., 2011, 43(1), 38-45.
[http://dx.doi.org/10.1016/j.nbd.2011.01.021] [PMID: 21296668]
Haass, C.; Selkoe, D.J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat. Rev. Mol. Cell Biol., 2007, 8(2), 101-112.
[http://dx.doi.org/10.1038/nrm2101] [PMID: 17245412]
Uddin, M.S.; Al Mamun, A.; Asaduzzaman, M.; Hosn, F.; Abu Sufian, M.; Takeda, S.; Herrera-Calderon, O.; Abdel-Daim, M.M.; Uddin, G.M.S.; Noor, M.A.A.; Begum, M.M.; Kabir, M.T.; Zaman, S.; Sarwar, M.S.; Rahman, M.M.; Rafe, M.R.; Hossain, M.F.; Hossain, M.S.; Ashraful Iqbal, M.; Sujan, M.A.R. Spectrum of disease and prescription pattern for outpatients with neurological disorders: an empirical pilot study in Bangladesh. Ann. Neurosci., 2018, 25(1), 25-37.
[http://dx.doi.org/10.1159/000481812] [PMID: 29887680]
Mamun, A.A.; Uddin, M.S.; Mathew, B.; Ashraf, G.M. Toxic tau: structural origins of tau aggregation in Alzheimer’s disease. Neural Regen. Res., 2020, 15(8), 1417-1420.
[http://dx.doi.org/10.4103/1673-5374.274329] [PMID: 31997800]
Lasagna-Reeves, C.A.; Castillo-Carranza, D.L.; Sengupta, U.; Sarmiento, J.; Troncoso, J.; Jackson, G.R.; Kayed, R. Identification of oligomers at early stages of tau aggregation in Alzheimer’s disease. FASEB J., 2012, 26(5), 1946-1959.
[http://dx.doi.org/10.1096/fj.11-199851] [PMID: 22253473]
Uddin, M.S.; Kabir, M.T.; Niaz, K.; Jeandet, P.; Clément, C.; Mathew, B.; Rauf, A.; Rengasamy, K.R.R.; Sobarzo-Sánchez, E.; Ashraf, G.M.; Aleya, L. Molecular insight into the therapeutic promise of flavonoids against Alzheimer’s disease. Molecules, 2020, 25(6), 1267.
[http://dx.doi.org/10.3390/molecules25061267] [PMID: 32168835]
Uddin, M.S.; Kabir, M.T.; Rahman, M.H.; Alim, M.A.; Rahman, M.M.; Khatkar, A.; Al Mamun, A.; Rauf, A.; Mathew, B.; Ashraf, G.M. Exploring the multifunctional neuroprotective promise of rasagiline derivatives for multi-dysfunctional Alzheimer’s disease. Curr. Pharm. Des, 2020, (Online ahead of print)
[PMID: 32250219]
Karsten, S.L.; Sang, T-K.; Gehman, L.T.; Chatterjee, S.; Liu, J.; Lawless, G.M.; Sengupta, S.; Berry, R.W.; Pomakian, J.; Oh, H.S.; Schulz, C.; Hui, K-S.; Wiedau-Pazos, M.; Vinters, H.V.; Binder, L.I.; Geschwind, D.H.; Jackson, G.R. A genomic screen for modifiers of tauopathy identifies puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration. Neuron, 2006, 51(5), 549-560.
[http://dx.doi.org/10.1016/j.neuron.2006.07.019] [PMID: 16950154]
Canu, N.; Dus, L.; Barbato, C.; Ciotti, M.T.; Brancolini, C.; Rinaldi, A.M.; Novak, M.; Cattaneo, A.; Bradbury, A.; Calissano, P. Tau cleavage and dephosphorylation in cerebellar granule neurons undergoing apoptosis. J. Neurosci., 1998, 18(18), 7061-7074.
[http://dx.doi.org/10.1523/JNEUROSCI.18-18-07061.1998] [PMID: 9736630]
Gamblin, T.C.; Chen, F.; Zambrano, A.; Abraha, A.; Lagalwar, S.; Guillozet, A.L.; Lu, M.; Fu, Y.; Garcia-Sierra, F.; LaPointe, N.; Miller, R.; Berry, R.W.; Binder, L.I.; Cryns, V.L. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2003, 100(17), 10032-10037.
[http://dx.doi.org/10.1073/pnas.1630428100] [PMID: 12888622]
Khlistunova, I.; Biernat, J.; Wang, Y.; Pickhardt, M.; von Bergen, M.; Gazova, Z.; Mandelkow, E.; Mandelkow, E-M. Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J. Biol. Chem., 2006, 281(2), 1205-1214.
[http://dx.doi.org/10.1074/jbc.M507753200] [PMID: 16246844]
Petrucelli, L.; Dickson, D.; Kehoe, K.; Taylor, J.; Snyder, H.; Grover, A.; De Lucia, M.; McGowan, E.; Lewis, J.; Prihar, G.; Kim, J.; Dillmann, W.H.; Browne, S.E.; Hall, A.; Voellmy, R.; Tsuboi, Y.; Dawson, T.M.; Wolozin, B.; Hardy, J.; Hutton, M. CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation. Hum. Mol. Genet., 2004, 13(7), 703-714.
[http://dx.doi.org/10.1093/hmg/ddh083] [PMID: 14962978]
Scaglione, K.M.; Basrur, V.; Ashraf, N.S.; Konen, J.R.; Elenitoba-Johnson, K.S.J.; Todi, S.V.; Paulson, H.L. The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus of substrates. J. Biol. Chem., 2013, 288(26), 18784-18788.
[http://dx.doi.org/10.1074/jbc.C113.477596] [PMID: 23696636]
Chesser, A.S.; Pritchard, S.M.; Johnson, G.V.W. Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease. Front. Neurol., 2013, 4, 122.
[http://dx.doi.org/10.3389/fneur.2013.00122] [PMID: 24027553]
Lee, M.J.; Lee, J.H.; Rubinsztein, D.C. Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system. Prog. Neurobiol., 2013, 105, 49-59.
[http://dx.doi.org/10.1016/j.pneurobio.2013.03.001] [PMID: 23528736]
Hamano, T.; Gendron, T.F.; Causevic, E.; Yen, S-H.; Lin, W-L.; Isidoro, C.; Deture, M.; Ko, L.W. Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression. Eur. J. Neurosci., 2008, 27(5), 1119-1130.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06084.x] [PMID: 18294209]
Dall’Armi, C.; Hurtado-Lorenzo, A.; Tian, H.; Morel, E.; Nezu, A.; Chan, R.B.; Yu, W.H.; Robinson, K.S.; Yeku, O.; Small, S.A.; Duff, K.; Frohman, M.A.; Wenk, M.R.; Yamamoto, A.; Di Paolo, G. The phospholipase D1 pathway modulates macroautophagy. Nat. Commun., 2010, 1, 142.
[http://dx.doi.org/10.1038/ncomms1144] [PMID: 21266992]
Dolan, P.J.; Johnson, G.V.W. A caspase cleaved form of tau is preferentially degraded through the autophagy pathway. J. Biol. Chem., 2010, 285(29), 21978-21987.
[http://dx.doi.org/10.1074/jbc.M110.110940] [PMID: 20466727]
Rodríguez-Martín, T.; Cuchillo-Ibáñez, I.; Noble, W.; Nyenya, F.; Anderton, B.H.; Hanger, D.P. Tau phosphorylation affects its axonal transport and degradation. Neurobiol. Aging, 2013, 34(9), 2146-2157.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.03.015] [PMID: 23601672]
Hoozemans, J.J.M.; van Haastert, E.S.; Nijholt, D.A.T.; Rozemuller, A.J.M.; Eikelenboom, P.; Scheper, W. The unfolded protein response is activated in pretangle neurons in Alzheimer’s disease hippocampus. Am. J. Pathol., 2009, 174(4), 1241-1251.
[http://dx.doi.org/10.2353/ajpath.2009.080814] [PMID: 19264902]
Hoozemans, J.J.M.; Veerhuis, R.; Van Haastert, E.S.; Rozemuller, J.M.; Baas, F.; Eikelenboom, P.; Scheper, W. The unfolded protein response is activated in Alzheimer’s disease. Acta Neuropathol., 2005, 110(2), 165-172.
[http://dx.doi.org/10.1007/s00401-005-1038-0] [PMID: 15973543]
Hamos, J.E.; Oblas, B.; Pulaski-Salo, D.; Welch, W.J.; Bole, D.G.; Drachman, D.A. Expression of heat shock proteins in Alzheimer’s disease. Neurology, 1991, 41(3), 345-350.
[http://dx.doi.org/10.1212/WNL.41.3.345] [PMID: 2005999]
Chang, R.C.C.; Suen, K.C.; Ma, C.H.; Elyaman, W.; Ng, H.K.; Hugon, J. Involvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2α in neuronal degeneration. J. Neurochem., 2002, 83(5), 1215-1225.
[http://dx.doi.org/10.1046/j.1471-4159.2002.01237.x] [PMID: 12437593]
Unterberger, U.; Höftberger, R.; Gelpi, E.; Flicker, H.; Budka, H.; Voigtländer, T. Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo. J. Neuropathol. Exp. Neurol., 2006, 65(4), 348-357.
[http://dx.doi.org/10.1097/01.jnen.0000218445.30535.6f] [PMID: 16691116]
Stutzbach, L.D.; Xie, S.X.; Naj, A.C.; Albin, R.; Gilman, S.; Lee, V.M.Y.; Trojanowski, J.Q.; Devlin, B.; Schellenberg, G.D. PSP Genetics Study Group The unfolded protein response is activated in disease-affected brain regions in progressive supranuclear palsy and Alzheimer’s disease. Acta Neuropathol. Commun., 2013, 1, 31.
[http://dx.doi.org/10.1186/2051-5960-1-31] [PMID: 24252572]
Baroja-Mazo, A.; Martín-Sánchez, F.; Gomez, A.I.; Martínez, C.M.; Amores-Iniesta, J.; Compan, V.; Barberà-Cremades, M.; Yagüe, J.; Ruiz-Ortiz, E.; Antón, J.; Buján, S.; Couillin, I.; Brough, D.; Arostegui, J.I.; Pelegrín, P. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat. Immunol., 2014, 15(8), 738-748.
[http://dx.doi.org/10.1038/ni.2919] [PMID: 24952504]
Venegas, C.; Kumar, S.; Franklin, B.S.; Dierkes, T.; Brinkschulte, R.; Tejera, D.; Vieira-Saecker, A.; Schwartz, S.; Santarelli, F.; Kummer, M.P.; Griep, A.; Gelpi, E.; Beilharz, M.; Riedel, D.; Golenbock, D.T.; Geyer, M.; Walter, J.; Latz, E.; Heneka, M.T. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease. Nature, 2017, 552(7685), 355-361.
[http://dx.doi.org/10.1038/nature25158] [PMID: 29293211]
Uddin, M.; Amran, M. Handbook of Research on Critical Examinations of Neurodegenerative Disorders; IGI Global: USA, 2018.
Uddin, M.S.; Mamun, A.A.; Jakaria, M.; Thangapandiyan, S.; Ahmad, J.; Rahman, M.A.; Mathew, B.; Abdel-Daim, M.M.; Aleya, L. Emerging promise of sulforaphane-mediated Nrf2 signaling cascade against neurological disorders. Sci. Total Environ., 2020, 707, 135624.
[http://dx.doi.org/10.1016/j.scitotenv.2019.135624] [PMID: 31784171]
Uddin, M.S.; Hossain, M.F.; Mamun, A.A.; Shah, M.A.; Hasana, S.; Bulbul, I.J.; Sarwar, M.S.; Mansouri, R.A.; Ashraf, G.M.; Rauf, A.; Abdel-Daim, M.M.; Bin-Jumah, M.N. Exploring the multimodal role of phytochemicals in the modulation of cellular signaling pathways to combat age-related neurodegeneration. Sci. Total Environ., 2020, 725, 138313.
[http://dx.doi.org/10.1016/j.scitotenv.2020.138313] [PMID: 32464743]
Polymeropoulos, M.H.; Lavedan, C.; Leroy, E.; Ide, S.E.; Dehejia, A.; Dutra, A.; Pike, B.; Root, H.; Rubenstein, J.; Boyer, R.; Stenroos, E.S.; Chandrasekharappa, S.; Athanassiadou, A.; Papapetropoulos, T.; Johnson, W.G.; Lazzarini, A.M.; Duvoisin, R.C.; Di Iorio, G.; Golbe, L.I.; Nussbaum, R.L. Mutation in the alpha-synuclein gene identified in families with parkinson’s disease. Science, 1997, 276, 2045-2047.
Krüger, R.; Kuhn, W.; Müller, T.; Woitalla, D.; Graeber, M.; Kösel, S.; Przuntek, H.; Epplen, J.T.; Schöls, L.; Riess, O. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat. Genet., 1998, 18(2), 106-108.
[http://dx.doi.org/10.1038/ng0298-106] [PMID: 9462735]
Kaur, G.; Behl, T.; Bungau, S.; Kumar, A.; Uddin, M.S.; Mehta, V.; Zengin, G.; Mathew, B.; Shah, M.A.; Arora, S. Dysregulation of the gut-brain axis, dysbiosis and influence of numerous factors on gut microbiota associated Parkinson’s disease. Curr. Neuropharmacol., 2020, 18.
[http://dx.doi.org/10.2174/1570159x18666200606233050 ] [PMID: 32580329]
Spillantini, M.G.; Schmidt, M.L.; Lee, V.M-Y.; Trojanowski, J.Q.; Jakes, R.; Goedert, M. α-synuclein in Lewy bodies. Nature, 1997, 388(6645), 839-840.
[http://dx.doi.org/10.1038/42166] [PMID: 9278044]
Baba, M.; Nakajo, S.; Tu, P.H.; Tomita, T.; Nakaya, K.; Lee, V.M.; Trojanowski, J.Q.; Iwatsubo, T. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am. J. Pathol., 1998, 152(4), 879-884.
[PMID: 9546347]
Seidel, K.; Schols, L.; Nuber, S.; Petrasch-Parwez, E.; Gierga, K.; Wszolek, Z.; Dickson, D.; Gai, W.; Bornemann, A.; Riess, O.; Rami, A.; den Dunnen, W.; Deller, T.; Rüb, U.; Krüger, R. First appraisal of brain pathology owing to a30p mutant Alpha-Synuclein. Ann. Neurol., 2010, 67(5), 684-699.
Imai, Y.; Soda, M.; Takahashi, R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem., 2000, 275(46), 35661-35664.
[http://dx.doi.org/10.1074/jbc.C000447200] [PMID: 10973942]
McLean, P.J.; Kawamata, H.; Hyman, B.T. Alpha-synuclein-enhanced green fluorescent protein fusion proteins form proteasome sensitive inclusions in primary neurons. Neuroscience, 2001, 104(3), 901-912.
[http://dx.doi.org/10.1016/S0306-4522(01)00113-0] [PMID: 11440819]
Bennett, M.C.; Bishop, J.F.; Leng, Y.; Chock, P.B.; Chase, T.N.; Mouradian, M.M. Degradation of α-synuclein by proteasome. J. Biol. Chem., 1999, 274(48), 33855-33858.
[http://dx.doi.org/10.1074/jbc.274.48.33855] [PMID: 10567343]
Tofaris, G.K.; Layfield, R.; Spillantini, M.G. alpha-synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett., 2001, 509(1), 22-26.
[http://dx.doi.org/10.1016/S0014-5793(01)03115-5] [PMID: 11734199]
Nakajima, T.; Takauchi, S.; Ohara, K.; Kokai, M.; Nishii, R.; Maeda, S.; Takanaga, A.; Tanaka, T.; Takeda, M.; Seki, M.; Morita, Y. α-synuclein-positive structures induced in leupeptin-infused rats. Brain Res., 2005, 1040(1-2), 73-80.
[http://dx.doi.org/10.1016/j.brainres.2005.01.099] [PMID: 15804428]
Machiya, Y.; Hara, S.; Arawaka, S.; Fukushima, S.; Sato, H.; Sakamoto, M.; Koyama, S.; Kato, T. Phosphorylated α-synuclein at Ser-129 is targeted to the proteasome pathway in a ubiquitin-independent manner. J. Biol. Chem., 2010, 285(52), 40732-40744.
[http://dx.doi.org/10.1074/jbc.M110.141952] [PMID: 20959456]
Mei, J.; Niu, C. Alterations of Hrd1 expression in various encephalic regional neurons in 6-OHDA model of Parkinson’s disease. Neurosci. Lett., 2010, 474(2), 63-68.
[http://dx.doi.org/10.1016/j.neulet.2010.02.033] [PMID: 20227462]
Nair, V.D.; McNaught, K.S.P.; González-Maeso, J.; Sealfon, S.C.; Olanow, C.W. p53 mediates nontranscriptional cell death in dopaminergic cells in response to proteasome inhibition. J. Biol. Chem., 2006, 281(51), 39550-39560.
[http://dx.doi.org/10.1074/jbc.M603950200] [PMID: 17060322]
Liani, E.; Eyal, A.; Avraham, E.; Shemer, R.; Szargel, R.; Berg, D.; Bornemann, A.; Riess, O.; Ross, C.A.; Rott, R.; Engelender, S. Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson’s disease. Proc. Natl. Acad. Sci. USA, 2004, 101(15), 5500-5505.
[http://dx.doi.org/10.1073/pnas.0401081101] [PMID: 15064394]
Lee, J.; Retamal, C.; Cuitiño, L.; Caruano-Yzermans, A.; Shin, J-E.; van Kerkhof, P.; Marzolo, M-P.; Bu, G. Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes. J. Biol. Chem., 2008, 283(17), 11501-11508.
[http://dx.doi.org/10.1074/jbc.M800642200] [PMID: 18276590]
Shin, Y.; Klucken, J.; Patterson, C.; Hyman, B.T.; McLean, P.J. The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates α-synuclein degradation decisions between proteasomal and lysosomal pathways. J. Biol. Chem., 2005, 280(25), 23727-23734.
[http://dx.doi.org/10.1074/jbc.M503326200] [PMID: 15845543]
Tofaris, G.K.; Kim, H.T.; Hourez, R.; Jung, J-W.; Kim, K.P.; Goldberg, A.L. Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway. Proc. Natl. Acad. Sci. USA, 2011, 108(41), 17004-17009.
[http://dx.doi.org/10.1073/pnas.1109356108] [PMID: 21953697]
Das, C.; Hoang, Q.Q.; Kreinbring, C.A.; Luchansky, S.J.; Meray, R.K.; Ray, S.S.; Lansbury, P.T.; Ringe, D.; Petsko, G.A. Structural basis for conformational plasticity of the Parkinson’s disease-associated ubiquitin hydrolase UCH-L1. Proc. Natl. Acad. Sci. USA, 2006, 103(12), 4675-4680.
[http://dx.doi.org/10.1073/pnas.0510403103] [PMID: 16537382]
Cartier, A.E.; Ubhi, K.; Spencer, B.; Vazquez-Roque, R.A.; Kosberg, K.A.; Fourgeaud, L.; Kanayson, P.; Patrick, C.; Rockenstein, E.; Patrick, G.N.; Masliah, E. Differential effects of UCHL1 modulation on alpha-synuclein in PD-like models of alpha-synucleinopathy. PLoS One, 2012, 7(4), e34713.
[http://dx.doi.org/10.1371/journal.pone.0034713] [PMID: 22514658]
Liu, Y.; Fallon, L.; Lashuel, H.A.; Liu, Z.; Lansbury, P.T., Jr The UCH-L1 gene encodes two opposing enzymatic activities that affect α-synuclein degradation and Parkinson’s disease susceptibility. Cell, 2002, 111(2), 209-218.
[http://dx.doi.org/10.1016/S0092-8674(02)01012-7] [PMID: 12408865]
Bedford, L.; Hay, D.; Devoy, A.; Paine, S.; Powe, D.G.; Seth, R.; Gray, T.; Topham, I.; Fone, K.; Rezvani, N.; Mee, M.; Soane, T.; Layfield, R.; Sheppard, P.W.; Ebendal, T.; Usoskin, D.; Lowe, J.; Mayer, R.J. Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies. J. Neurosci., 2008, 28(33), 8189-8198.
[http://dx.doi.org/10.1523/JNEUROSCI.2218-08.2008] [PMID: 18701681]
Lindersson, E.; Beedholm, R.; Højrup, P.; Moos, T.; Gai, W.; Hendil, K.B.; Jensen, P.H. Proteasomal inhibition by α-synuclein filaments and oligomers. J. Biol. Chem., 2004, 279(13), 12924-12934.
[http://dx.doi.org/10.1074/jbc.M306390200] [PMID: 14711827]
McNaught, K.S.; Jenner, P. Proteasomal function is impaired in substantia nigra in Parkinson’s disease. Neurosci. Lett., 2001, 297(3), 191-194.
[http://dx.doi.org/10.1016/S0304-3940(00)01701-8] [PMID: 11137760]
Cuervo, A.M.; Stefanis, L.; Fredenburg, R.; Lansbury, P.T.; Sulzer, D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science, 2004, 305, 1292-1295.
Vogiatzi, T.; Xilouri, M.; Vekrellis, K.; Stefanis, L. Wild type α-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J. Biol. Chem., 2008, 283(35), 23542-23556.
[http://dx.doi.org/10.1074/jbc.M801992200] [PMID: 18566453]
Malkus, K.A.; Ischiropoulos, H. Regional deficiencies in chaperone-mediated autophagy underlie α-synuclein aggregation and neurodegeneration. Neurobiol. Dis., 2012, 46(3), 732-744.
[http://dx.doi.org/10.1016/j.nbd.2012.03.017] [PMID: 22426402]
Ciechanover, A.; Kwon, Y.T. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp. Mol. Med., 2015, 47, e147.
[http://dx.doi.org/10.1038/emm.2014.117] [PMID: 25766616]
Sevlever, D.; Jiang, P.; Yen, S-H.C.; Cathepsin, D. Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species. Biochemistry, 2008, 47(36), 9678-9687.
[http://dx.doi.org/10.1021/bi800699v] [PMID: 18702517]
Cullen, V.; Lindfors, M.; Ng, J.; Paetau, A.; Swinton, E.; Kolodziej, P.; Boston, H.; Saftig, P.; Woulfe, J.; Feany, M.B.; Myllykangas, L.; Schlossmacher, M.G.; Tyynelä, J.; Cathepsin, D. Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo. Mol. Brain, 2009, 2, 5.
[http://dx.doi.org/10.1186/1756-6606-2-5] [PMID: 19203374]
Paxinou, E.; Chen, Q.; Weisse, M.; Giasson, B.I.; Norris, E.H.; Rueter, S.M.; Trojanowski, J.Q.; Lee, V.M.; Ischiropoulos, H. Induction of alpha-synuclein aggregation by intracellular nitrative insult. J. Neurosci., 2001, 21(20), 8053-8061.
[http://dx.doi.org/10.1523/JNEUROSCI.21-20-08053.2001] [PMID: 11588178]
Spencer, B.; Potkar, R.; Trejo, M.; Rockenstein, E.; Patrick, C.; Gindi, R.; Adame, A.; Wyss-Coray, T.; Masliah, E. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson’s and Lewy body diseases. J. Neurosci., 2009, 29(43), 13578-13588.
[http://dx.doi.org/10.1523/JNEUROSCI.4390-09.2009] [PMID: 19864570]
Hoozemans, J.J.M.; van Haastert, E.S.; Eikelenboom, P.; de Vos, R.A.I.; Rozemuller, J.M.; Scheper, W. Activation of the unfolded protein response in Parkinson’s disease. Biochem. Biophys. Res. Commun., 2007, 354(3), 707-711.
[http://dx.doi.org/10.1016/j.bbrc.2007.01.043] [PMID: 17254549]
Makioka, K.; Yamazaki, T.; Fujita, Y.; Takatama, M.; Nakazato, Y.; Okamoto, K. Involvement of endoplasmic reticulum stress defined by activated unfolded protein response in multiple system atrophy. J. Neurol. Sci., 2010, 297(1-2), 60-65.
[http://dx.doi.org/10.1016/j.jns.2010.06.019] [PMID: 20667553]
Stefanis, L.; Larsen, K.E.; Rideout, H.J.; Sulzer, D.; Greene, L.A. Expression of A53T mutant but not wild-type α-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J. Neurosci., 2001, 21(24), 9549-9560.
[http://dx.doi.org/10.1523/JNEUROSCI.21-24-09549.2001] [PMID: 11739566]
Cooper, A.A.; Gitler, A.D.; Cashikar, A.; Haynes, C.M.; Hill, K.J.; Bhullar, B.; Liu, K.; Xu, K.; Strathearn, K.E.; Liu, F.; Cao, S.; Caldwell, K.A.; Caldwell, G.A.; Marsischky, G.; Kolodner, R.D.; LaBaer, J.; Rochet, J.C.; Bonini, N.M.; Lindquist, S. α-synuclein blocks er-golgi traffic and rab1 rescues neuron loss in parkinson’s models. Science, 2006, 313, 324-328.
Rahman, M.A.; Rahman, M.R.; Zaman, T.; Uddin, M.S.; Islam, R.; Abdel-Daim, M.M.; Rhim, H. Emerging potential of naturally occurring autophagy modulators against neurodegeneration. Curr. Pharm. Des., 2020, 26(7), 772-779.
[http://dx.doi.org/10.2174/1381612826666200107142541] [PMID: 31914904]
Munoz-Sanjuan, I.; Bates, G.P. The importance of integrating basic and clinical research toward the development of new therapies for Huntington disease. J. Clin. Invest., 2011, 121(2), 476-483.
[http://dx.doi.org/10.1172/JCI45364] [PMID: 21285520]
Walker, F.O. Huntington’s disease. Lancet, 2007, 369(9557), 218-228.
[http://dx.doi.org/10.1016/S0140-6736(07)60111-1] [PMID: 17240289]
Arrasate, M.; Finkbeiner, S. Protein aggregates in Huntington’s disease. Exp. Neurol., 2012, 238(1), 1-11.
[http://dx.doi.org/10.1016/j.expneurol.2011.12.013] [PMID: 22200539]
Warby, S.C.; Visscher, H.; Collins, J.A.; Doty, C.N.; Carter, C.; Butland, S.L.; Hayden, A.R.; Kanazawa, I.; Ross, C.J.; Hayden, M.R. HTT haplotypes contribute to differences in Huntington disease prevalence between Europe and East Asia. Eur. J. Hum. Genet., 2011, 19(5), 561-566.
[http://dx.doi.org/10.1038/ejhg.2010.229] [PMID: 21248742]
Williams, A.J.; Paulson, H.L. Polyglutamine neurodegeneration: protein misfolding revisited. Trends Neurosci., 2008, 31(10), 521-528.
[http://dx.doi.org/10.1016/j.tins.2008.07.004] [PMID: 18778858]
Soto, C. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. Neurosci., 2003, 4(1), 49-60.
[http://dx.doi.org/10.1038/nrn1007] [PMID: 12511861]
Miller, J.; Arrasate, M.; Brooks, E.; Libeu, C.P.; Legleiter, J.; Hatters, D.; Curtis, J.; Cheung, K.; Krishnan, P.; Mitra, S.; Widjaja, K.; Shaby, B.A.; Lotz, G.P.; Newhouse, Y.; Mitchell, E.J.; Osmand, A.; Gray, M.; Thulasiramin, V.; Saudou, F.; Segal, M.; Yang, X.W.; Masliah, E.; Thompson, L.M.; Muchowski, P.J.; Weisgraber, K.H.; Finkbeiner, S. Identifying polyglutamine protein species in situ that best predict neurodegeneration. Nat. Chem. Biol., 2011, 7(12), 925-934.
[http://dx.doi.org/10.1038/nchembio.694] [PMID: 22037470]
Kar, K.; Jayaraman, M.; Sahoo, B.; Kodali, R.; Wetzel, R. Critical nucleus size for disease-related polyglutamine aggregation is repeat-length dependent. Nat. Struct. Mol. Biol., 2011, 18(3), 328-336.
[http://dx.doi.org/10.1038/nsmb.1992] [PMID: 21317897]
Qi, L.; Zhang, X-D.; Wu, J-C.; Lin, F.; Wang, J.; DiFiglia, M.; Qin, Z-H. The role of chaperone-mediated autophagy in huntingtin degradation. PLoS One, 2012, 7(10), e46834.
[http://dx.doi.org/10.1371/journal.pone.0046834] [PMID: 23071649]
DiFiglia, M.; Sapp, E.; Chase, K.O.; Davies, S.W.; Bates, G.P.; Vonsattel, J.P.; Aronin, N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 1997, 277, 1990-1993.
Hipp, M.S.; Patel, C.N.; Bersuker, K.; Riley, B.E.; Kaiser, S.E.; Shaler, T.A.; Brandeis, M.; Kopito, R.R. Indirect inhibition of 26S proteasome activity in a cellular model of Huntington’s disease. J. Cell Biol., 2012, 196(5), 573-587.
[http://dx.doi.org/10.1083/jcb.201110093] [PMID: 22371559]
Jeong, H.; Then, F.; Melia, T.J., Jr; Mazzulli, J.R.; Cui, L.; Savas, J.N.; Voisine, C.; Paganetti, P.; Tanese, N.; Hart, A.C.; Yamamoto, A.; Krainc, D. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell, 2009, 137(1), 60-72.
[http://dx.doi.org/10.1016/j.cell.2009.03.018] [PMID: 19345187]
Martinez-Vicente, M.; Talloczy, Z.; Wong, E.; Tang, G.; Koga, H.; Kaushik, S.; de Vries, R.; Arias, E.; Harris, S.; Sulzer, D.; Cuervo, A.M. Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease. Nat. Neurosci., 2010, 13(5), 567-576.
[http://dx.doi.org/10.1038/nn.2528] [PMID: 20383138]
Wong, E.; Cuervo, A.M. Autophagy gone awry in neurodegenerative diseases. Nat. Neurosci., 2010, 13(7), 805-811.
[http://dx.doi.org/10.1038/nn.2575] [PMID: 20581817]
Lee, H.; Noh, J-Y.; Oh, Y.; Kim, Y.; Chang, J-W.; Chung, C-W.; Lee, S-T.; Kim, M.; Ryu, H.; Jung, Y-K. IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux. Hum. Mol. Genet., 2012, 21(1), 101-114.
[http://dx.doi.org/10.1093/hmg/ddr445] [PMID: 21954231]
Ravikumar, B.; Vacher, C.; Berger, Z.; Davies, J.E.; Luo, S.; Oroz, L.G.; Scaravilli, F.; Easton, D.F.; Duden, R.; O’Kane, C.J.; Rubinsztein, D.C. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet., 2004, 36(6), 585-595.
[http://dx.doi.org/10.1038/ng1362] [PMID: 15146184]
Shibata, M.; Lu, T.; Furuya, T.; Degterev, A.; Mizushima, N.; Yoshimori, T.; MacDonald, M.; Yankner, B.; Yuan, J. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem., 2006, 281(20), 14474-14485.
[http://dx.doi.org/10.1074/jbc.M600364200] [PMID: 16522639]
Moughamian, A.J.; Holzbaur, E.L.F. Dynactin is required for transport initiation from the distal axon. Neuron, 2012, 74(2), 331-343.
[http://dx.doi.org/10.1016/j.neuron.2012.02.025] [PMID: 22542186]
Ikenaka, K.; Kawai, K.; Katsuno, M.; Huang, Z.; Jiang, Y-M.; Iguchi, Y.; Kobayashi, K.; Kimata, T.; Waza, M.; Tanaka, F.; Mori, I.; Sobue, G. dnc-1/dynactin 1 knockdown disrupts transport of autophagosomes and induces motor neuron degeneration. PLoS One, 2013, 8(2), e54511.
[http://dx.doi.org/10.1371/journal.pone.0054511] [PMID: 23408943]
Fecto, F.; Yan, J.; Vemula, S.P.; Liu, E.; Yang, Y.; Chen, W.; Zheng, J.G.; Shi, Y.; Siddique, N.; Arrat, H.; Donkervoort, S.; Ajroud-Driss, S.; Sufit, R.L.; Heller, S.L.; Deng, H-X.; Siddique, T. SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch. Neurol., 2011, 68(11), 1440-1446.
[http://dx.doi.org/10.1001/archneurol.2011.250] [PMID: 22084127]
Fecto, F.; Siddique, T. UBQLN2/P62 cellular recycling pathways in amyotrophic lateral sclerosis and frontotemporal dementia. Muscle Nerve, 2012, 45(2), 157-162.
[http://dx.doi.org/10.1002/mus.23278] [PMID: 22246868]
Guo, Y.; Li, C.; Wu, D.; Wu, S.; Yang, C.; Liu, Y.; Wu, H.; Li, Z. Ultrastructural diversity of inclusions and aggregations in the lumbar spinal cord of SOD1-G93A transgenic mice. Brain Res., 2010, 1353, 234-244.
[http://dx.doi.org/10.1016/j.brainres.2010.07.025] [PMID: 20637744]
Fukai, T.; Ushio-Fukai, M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid. Redox Signal., 2011, 15(6), 1583-1606.
[http://dx.doi.org/10.1089/ars.2011.3999] [PMID: 21473702]
Beleza-Meireles, A.; Al-Chalabi, A. Genetic studies of amyotrophic lateral sclerosis: controversies and perspectives. Amyotroph. Lateral Scler., 2009, 10(1), 1-14.
[http://dx.doi.org/10.1080/17482960802585469] [PMID: 19110986]
Buratti, E.; Baralle, F.E. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front. Biosci., 2008, 13, 867-878.
[http://dx.doi.org/10.2741/2727] [PMID: 17981595]
Johnson, B.S.; Snead, D.; Lee, J.J.; McCaffery, J.M.; Shorter, J.; Gitler, A.D. TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J. Biol. Chem., 2009, 284(30), 20329-20339.
[http://dx.doi.org/10.1074/jbc.M109.010264] [PMID: 19465477]
Mendonça, D.M.F.; Chimelli, L.; Martinez, A.M.B. Expression of ubiquitin and proteasome in motorneurons and astrocytes of spinal cords from patients with amyotrophic lateral sclerosis. Neurosci. Lett., 2006, 404(3), 315-319.
[http://dx.doi.org/10.1016/j.neulet.2006.06.009] [PMID: 16806703]
Sasaki, S. Endoplasmic reticulum stress in motor neurons of the spinal cord in sporadic amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol., 2010, 69(4), 346-355.
[http://dx.doi.org/10.1097/NEN.0b013e3181d44992] [PMID: 20448480]
Leigh, P.N. Whitwell, H.; Garofalo, O.; Buller, J.; Swash, M.; Martin, J.E.; Gallo, J.-M.; Weller, R.O.; Anderton, B.H. Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. morphology, distribution, and specificity. Brain, 1991, 114, 775-788.
Bruijn, L.I.; Becher, M.W.; Lee, M.K.; Anderson, K.L.; Jenkins, N.A.; Copeland, N.G.; Sisodia, S.S.; Rothstein, J.D.; Borchelt, D.R.; Price, D.L.; Cleveland, D.W. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron, 1997, 18(2), 327-338.
[http://dx.doi.org/10.1016/S0896-6273(00)80272-X] [PMID: 9052802]
Bendotti, C.; Atzori, C.; Piva, R.; Tortarolo, M.; Strong, M.J.; DeBiasi, S.; Migheli, A. Activated p38MAPK is a novel component of the intracellular inclusions found in human amyotrophic lateral sclerosis and mutant SOD1 transgenic mice. J. Neuropathol. Exp. Neurol., 2004, 63(2), 113-119.
[http://dx.doi.org/10.1093/jnen/63.2.113] [PMID: 14989597]
Watanabe, M.; Dykes-Hoberg, M.; Culotta, V.C.; Price, D.L.; Wong, P.C.; Rothstein, J.D. Histological evidence of protein aggregation in mutant SOD1 transgenic mice and in amyotrophic lateral sclerosis neural tissues. Neurobiol. Dis., 2001, 8(6), 933-941.
[http://dx.doi.org/10.1006/nbdi.2001.0443] [PMID: 11741389]
Morimoto, N.; Nagai, M.; Ohta, Y.; Miyazaki, K.; Kurata, T.; Morimoto, M.; Murakami, T.; Takehisa, Y.; Ikeda, Y.; Kamiya, T.; Abe, K. Increased autophagy in transgenic mice with a G93A mutant SOD1 gene. Brain Res., 2007, 1167, 112-117.
[http://dx.doi.org/10.1016/j.brainres.2007.06.045] [PMID: 17689501]
Di Noto, L.; Whitson, L.J.; Cao, X.; Hart, P.J.; Levine, R.L. Proteasomal degradation of mutant superoxide dismutases linked to amyotrophic lateral sclerosis. J. Biol. Chem., 2005, 280(48), 39907-39913.
[http://dx.doi.org/10.1074/jbc.M506247200] [PMID: 16195234]
Hoffman, E.K.; Wilcox, H.M.; Scott, R.W.; Siman, R. Proteasome inhibition enhances the stability of mouse Cu/Zn superoxide dismutase with mutations linked to familial amyotrophic lateral sclerosis. J. Neurol. Sci., 1996, 139(1), 15-20.
[http://dx.doi.org/10.1016/0022-510X(96)00031-7] [PMID: 8836967]
Carra, S.; Crippa, V.; Rusmini, P.; Boncoraglio, A.; Minoia, M.; Giorgetti, E.; Kampinga, H.H.; Poletti, A. Alteration of protein folding and degradation in motor neuron diseases: Implications and protective functions of small heat shock proteins. Prog. Neurobiol., 2012, 97(2), 83-100.
[http://dx.doi.org/10.1016/j.pneurobio.2011.09.009] [PMID: 21971574]
Carra, S.; Rusmini, P.; Crippa, V.; Giorgetti, E.; Boncoraglio, A.; Cristofani, R.; Naujock, M.; Meister, M.; Minoia, M.; Kampinga, H.H.; Poletti, A. Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2013, 368(1617), 20110409.
[http://dx.doi.org/10.1098/rstb.2011.0409] [PMID: 23530259]
Zhang, X.; Li, L.; Chen, S.; Yang, D.; Wang, Y.; Zhang, X.; Wang, Z.; Le, W. Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Autophagy, 2011, 7(4), 412-425.
[http://dx.doi.org/10.4161/auto.7.4.14541] [PMID: 21193837]
Hyun, D-H.; Lee, M.; Halliwell, B.; Jenner, P. Proteasomal inhibition causes the formation of protein aggregates containing a wide range of proteins, including nitrated proteins. J. Neurochem., 2003, 86(2), 363-373.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01841.x] [PMID: 12871577]
Puttaparthi, K.; Wojcik, C.; Rajendran, B.; DeMartino, G.N.; Elliott, J.L. Aggregate formation in the spinal cord of mutant SOD1 transgenic mice is reversible and mediated by proteasomes. J. Neurochem., 2003, 87(4), 851-860.
[http://dx.doi.org/10.1046/j.1471-4159.2003.02028.x] [PMID: 14622116]
Crippa, V.; Sau, D.; Rusmini, P.; Boncoraglio, A.; Onesto, E.; Bolzoni, E.; Galbiati, M.; Fontana, E.; Marino, M.; Carra, S.; Bendotti, C.; De Biasi, S.; Poletti, A. The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum. Mol. Genet., 2010, 19(17), 3440-3456.
[http://dx.doi.org/10.1093/hmg/ddq257] [PMID: 20570967]
Atkin, J.D.; Farg, M.A.; Walker, A.K.; McLean, C.; Tomas, D.; Horne, M.K. Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis. Neurobiol. Dis., 2008, 30(3), 400-407.
[http://dx.doi.org/10.1016/j.nbd.2008.02.009] [PMID: 18440237]
Hetz, C.; Thielen, P.; Matus, S.; Nassif, M.; Court, F.; Kiffin, R.; Martinez, G.; Cuervo, A.M.; Brown, R.H.; Glimcher, L.H. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev., 2009, 23(19), 2294-2306.
[http://dx.doi.org/10.1101/gad.1830709] [PMID: 19762508]
Ito, Y.; Yamada, M.; Tanaka, H.; Aida, K.; Tsuruma, K.; Shimazawa, M.; Hozumi, I.; Inuzuka, T.; Takahashi, H.; Hara, H. Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice. Neurobiol. Dis., 2009, 36(3), 470-476.
[http://dx.doi.org/10.1016/j.nbd.2009.08.013] [PMID: 19733664]
Nagata, T.; Ilieva, H.; Murakami, T.; Shiote, M.; Narai, H.; Ohta, Y.; Hayashi, T.; Shoji, M.; Abe, K.; Increased, E.R. Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis. Neurol. Res., 2007, 29(8), 767-771.
[http://dx.doi.org/10.1179/016164107X229803] [PMID: 17672929]
Kovacs, G.G.; Budka, H. Prion diseases: from protein to cell pathology. Am. J. Pathol., 2008, 172(3), 555-565.
[http://dx.doi.org/10.2353/ajpath.2008.070442] [PMID: 18245809]
Lugaresi, E.; Medori, R.; Montagna, P.; Baruzzi, A.; Cortelli, P.; Lugaresi, A.; Tinuper, P.; Zucconi, M.; Gambetti, P. Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N. Engl. J. Med., 1986, 315(16), 997-1003.
[http://dx.doi.org/10.1056/NEJM198610163151605] [PMID: 3762620]
Gajdusek, D.C.; Gibbs, C.J.; Alpers, M. Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature, 1966, 209(5025), 794-796.
[http://dx.doi.org/10.1038/209794a0] [PMID: 5922150]
Gibbs, C.J.; Gajdusek, D.C.; Asher, D.M.; Alpers, M.P.; Beck, E.; Daniel, P.M.; Matthews, W.B. Creutzfeldt-jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science, 1968, 161, 388-389.
Masters, C.L.; Gajdusek, D.C.; Gibbs, C.J. Jr Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Sträussler syndrome with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies. Brain, 1981, 104(3), 559-588.
[http://dx.doi.org/10.1093/brain/104.3.559] [PMID: 6791762]
Legname, G.; Baskakov, I.V.; Nguyen, H.O.B.; Riesner, D.; Cohen, F.E.; DeArmond, S.J.; Prusiner, S.B. Synthetic mammalian prions. Science, 2004, 305, 673-676.
Castilla, J.; Saá, P.; Hetz, C.; Soto, C. In vitro generation of infectious scrapie prions. Cell, 2005, 121(2), 195-206.
[http://dx.doi.org/10.1016/j.cell.2005.02.011] [PMID: 15851027]
Wang, F.; Wang, X.; Yuan, C.G.; Ma, J. Generating a prion with bacterially expressed recombinant prion protein. Science, 2010, 327, 1132-1135.
Saborio, G.P.; Permanne, B.; Soto, C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature, 2001, 411(6839), 810-813.
[http://dx.doi.org/10.1038/35081095] [PMID: 11459061]
Soto, C. Transmissible proteins: expanding the prion heresy. Cell, 2012, 149(5), 968-977.
[http://dx.doi.org/10.1016/j.cell.2012.05.007] [PMID: 22632966]
Shorter, J.; Lindquist, S. Hsp104 catalyzes formation and elimination of self-replicating sup35 prion conformers. Science, 2004, 304, 1793-1797.
DebBurman S.K.; Raymond, G.J.; Caughey, B.; Lindquist, S. Chaperone-supervised conversion of prion protein to its protease-resistant form. Proc. Natl. Acad. Sci. USA, 1997, 94(25), 13938-13943.
[http://dx.doi.org/10.1073/pnas.94.25.13938] [PMID: 9391131]
Wilkins, S.; Choglay, A.A.; Chapple, J.P.; van der Spuy, J.; Rhie, A.; Birkett, C.R.; Cheetham, M.E. The binding of the molecular chaperone Hsc70 to the prion protein PrP is modulated by pH and copper. Int. J. Biochem. Cell Biol., 2010, 42(7), 1226-1232.
[http://dx.doi.org/10.1016/j.biocel.2010.04.013] [PMID: 20434583]
Förster, A.; Masters, E.I.; Whitby, F.G.; Robinson, H.; Hill, C.P. The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions. Mol. Cell, 2005, 18(5), 589-599.
[http://dx.doi.org/10.1016/j.molcel.2005.04.016] [PMID: 15916965]
Kristiansen, M.; Deriziotis, P.; Dimcheff, D.E.; Jackson, G.S.; Ovaa, H.; Naumann, H.; Clarke, A.R.; van Leeuwen, F.W.B.; Menéndez-Benito, V.; Dantuma, N.P.; Portis, J.L.; Collinge, J.; Tabrizi, S.J. Disease-associated prion protein oligomers inhibit the 26S proteasome. Mol. Cell, 2007, 26(2), 175-188.
[http://dx.doi.org/10.1016/j.molcel.2007.04.001] [PMID: 17466621]
Deriziotis, P.; André, R.; Smith, D.M.; Goold, R.; Kinghorn, K.J.; Kristiansen, M.; Nathan, J.A.; Rosenzweig, R.; Krutauz, D.; Glickman, M.H.; Collinge, J.; Goldberg, A.L.; Tabrizi, S.J. Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry. EMBO J., 2011, 30(15), 3065-3077.
[http://dx.doi.org/10.1038/emboj.2011.224] [PMID: 21743439]
Gregori, L.; Fuchs, C.; Figueiredo-Pereira, M.E.; Van Nostrand, W.E.; Goldgaber, D. Amyloid β-protein inhibits ubiquitin-dependent protein degradation in vitro. J. Biol. Chem., 1995, 270(34), 19702-19708.
[http://dx.doi.org/10.1074/jbc.270.34.19702] [PMID: 7649980]
Boellaard, J.W.; Kao, M.; Schlote, W.; Diringer, H. Neuronal autophagy in experimental scrapie. Acta Neuropathol., 1991, 82(3), 225-228.
[http://dx.doi.org/10.1007/BF00294449] [PMID: 1927279]
Sikorska, B.; Liberski, P.P.; Brown, P. Neuronal autophagy and aggresomes constitute a consistent part of neurodegeneration in experimental scrapie. Folia Neuropathol., 2007, 45(4), 170-178.
[PMID: 18176890]
Mishra, R.S.; Bose, S.; Gu, Y.; Li, R.; Singh, N. Aggresome formation by mutant prion proteins: the unfolding role of proteasomes in familial prion disorders. J. Alzheimers Dis., 2003, 5(1), 15-23.
[http://dx.doi.org/10.3233/JAD-2003-5103] [PMID: 12590162]
Heitz, S.; Grant, N.J.; Bailly, Y. Doppel induces autophagic stress in prion protein-deficient Purkinje cells. Autophagy, 2009, 5(3), 422-424.
[http://dx.doi.org/10.4161/auto.5.3.7882] [PMID: 19320049]
Heiseke, A.; Aguib, Y.; Schatzl, H.M. Autophagy, prion infection and their mutual interactions. Curr. Issues Mol. Biol., 2010, 12(2), 87-97.
[http://dx.doi.org/10.21775/9781912530076.03] [PMID: 19767652]
Aguib, Y.; Heiseke, A.; Gilch, S.; Riemer, C.; Baier, M.; Schätzl, H.M.; Ertmer, A. Autophagy induction by trehalose counteracts cellular prion infection. Autophagy, 2009, 5(3), 361-369.
[http://dx.doi.org/10.4161/auto.5.3.7662] [PMID: 19182537]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [2025 - 2043]
Pages: 19
DOI: 10.2174/1568026620666200618114924
Price: $65

Article Metrics

PDF: 44