Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

Author(s): John H. Miller*, Viswanath Das

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 35 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

Keywords: Alzheimer's disease, davunetide, epothilone D, microtubule stabilizing agents, parkinson's disease, tauopathies, triazolopyrimidine.

[1]
Orr ME, Sullivan AC, Frost B. A brief overview of tauopathy: Causes, consequences, and therapeutic strategies. Trends Pharmacol Sci 2017; 38(7): 637-48.
[http://dx.doi.org/10.1016/j.tips.2017.03.011] [PMID: 28455089]
[2]
Kneynsberg A, Combs B, Christensen K, Morfini G, Kanaan NM. Axonal degeneration in tauopathies: Disease relevance and underlying mechanisms. Front Neurosci 2017; 11: 572.
[http://dx.doi.org/10.3389/fnins.2017.00572] [PMID: 29089864]
[3]
Wheeler S, Sillence DJ. Niemann-Pick type C disease: cellular pathology and pharmacotherapy. J Neurochem 2019. Epub ahead of print
[http://dx.doi.org/10.1111/jnc.14895] [PMID: 31608980]
[4]
Zhang B, Maiti A, Shively S, et al. Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model. Proc Natl Acad Sci USA 2005; 102(1): 227-31.
[http://dx.doi.org/10.1073/pnas.0406361102] [PMID: 15615853]
[5]
Brunden KR, Yao Y, Potuzak JS, et al. The characterization of microtubule-stabilizing drugs as possible therapeutic agents for Alzheimer’s disease and related tauopathies. Pharmacol Res 2011; 63(4): 341-51.
[http://dx.doi.org/10.1016/j.phrs.2010.12.002] [PMID: 21163349]
[6]
Brunden KR, Trojanowski JQ, Lee VM. Advances in tau-focused drug discovery for Alzheimer’s disease and related tauopathies. Nat Rev Drug Discov 2009; 8(10): 783-93.
[http://dx.doi.org/10.1038/nrd2959] [PMID: 19794442]
[7]
Brunden KR, Trojanowski JQ, Smith AB III, Lee VM, Ballatore C. Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease. Bioorg Med Chem 2014; 22(18): 5040-9.
[http://dx.doi.org/10.1016/j.bmc.2013.12.046] [PMID: 24433963]
[8]
Brunden KR, Lee VM, Smith AB III, Trojanowski JQ, Ballatore C. Altered microtubule dynamics in neurodegenerative disease: Therapeutic potential of microtubule-stabilizing drugs. Neurobiol Dis 2017; 105: 328-35.
[http://dx.doi.org/10.1016/j.nbd.2016.12.021] [PMID: 28012891]
[9]
Ballatore C, Brunden KR, Huryn DM, Trojanowski JQ, Lee VM, Smith AB III. Microtubule stabilizing agents as potential treatment for Alzheimer’s disease and related neurodegenerative tauopathies. J Med Chem 2012; 55(21): 8979-96.
[http://dx.doi.org/10.1021/jm301079z] [PMID: 23020671]
[10]
Spillantini MG, Goedert M. Tau pathology and neurodegeneration. Lancet Neurol 2013; 12(6): 609-22.
[http://dx.doi.org/10.1016/S1474-4422(13)70090-5] [PMID: 23684085]
[11]
Khanna MR, Kovalevich J, Lee VM, Trojanowski JQ, Brunden KR. Therapeutic strategies for the treatment of tauopathies: Hopes and challenges. Alzheimers Dement 2016; 12(10): 1051-65.
[http://dx.doi.org/10.1016/j.jalz.2016.06.006] [PMID: 27751442]
[12]
Rosenblum WI. Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult. Neurobiol Aging 2014; 35(5): 969-74.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.10.085] [PMID: 24210593]
[13]
Cao YN1. Zheng LL2, Wang D3, Liang XX4, Gao F5, Zhou XL Recent advances in microtubule-stabilizing agents. Eur J Med Chem 2018; 143: 806-28.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.062]
[14]
Miller JH, Field JJ, Kanakkanthara A, Owen JG, Singh AJ, Northcote PT. Marine invertebrate natural products that target microtubules. J Nat Prod 2018; 81(3): 691-702.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00964] [PMID: 29431439]
[15]
Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979; 277(5698): 665-7.
[http://dx.doi.org/10.1038/277665a0] [PMID: 423966]
[16]
Yang CH, Horwitz SB. Taxol®: The first microtubule stabilizing agent. Int J Mol Sci 2017; 18(8)E1733
[http://dx.doi.org/10.3390/ijms18081733] [PMID: 28792473]
[17]
Tinley TL, Randall-Hlubek DA, Leal RM, et al. Taccalonolides E and A: Plant-derived steroids with microtubule-stabilizing activity. Cancer Res 2003; 63(12): 3211-20.
[PMID: 12810650]
[18]
Li J, Risinger AL, Mooberry SL. Taccalonolide microtubule stabilizers. Bioorg Med Chem 2014; 22(18): 5091-6.
[http://dx.doi.org/10.1016/j.bmc.2014.01.012] [PMID: 24491636]
[19]
Ye K, Ke Y, Keshava N, et al. Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells. Proc Natl Acad Sci USA 1998; 95(4): 1601-6.
[http://dx.doi.org/10.1073/pnas.95.4.1601] [PMID: 9465062]
[20]
Bollag DM, McQueney PA, Zhu J, et al. Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 1995; 55(11): 2325-33.
[PMID: 7757983]
[21]
Isbrucker RA, Cummins J, Pomponi SA, Longley RE, Wright AE. Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin. Biochem Pharmacol 2003; 66(1): 75-82.
[http://dx.doi.org/10.1016/S0006-2952(03)00192-8] [PMID: 12818367]
[22]
ter Haar E, Kowalski RJ, Hamel E, et al. Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochemistry 1996; 35(1): 243-50.
[http://dx.doi.org/10.1021/bi9515127] [PMID: 8555181]
[23]
Mooberry SL, Tien G, Hernandez AH, Plubrukarn A, Davidson BS. Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. Cancer Res 1999; 59(3): 653-60.
[PMID: 9973214]
[24]
Hood KA, West LM, Rouwé B, et al. Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule- stabilizing activity. Cancer Res 2002; 62(12): 3356-60.
[PMID: 12067973]
[25]
Kanakkanthara A, Northcote PT, Miller JH. Peloruside A: a lead non-taxoid-site microtubule-stabilizing agent with potential activity against cancer, neurodegeneration, and autoimmune disease. Nat Prod Rep 2016; 33(4): 549-61.
[http://dx.doi.org/10.1039/C5NP00146C] [PMID: 26867978]
[26]
Field JJ, Northcote PT, Paterson I, Altmann KH, Díaz JF, Miller JH. Zampanolide, a microtubule-stabilizing agent, is active in resistant cancer cells and inhibits cell migration. Int J Mol Sci 2017; 18(5)E971
[http://dx.doi.org/10.3390/ijms18050971] [PMID: 28467385]
[27]
Ni R, Kindler DR, Waag R, et al. fMRI reveals mitigation of cerebrovascular dysfunction by bradykinin receptors 1 and 2 inhibitor noscapine in a mouse model of cerebral amyloidosis. Front Aging Neurosci 2019; 11: 27.
[http://dx.doi.org/10.3389/fnagi.2019.00027] [PMID: 30890928]
[28]
Matsuoka Y, Jouroukhin Y, Gray AJ, et al. A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer’s disease. J Pharmacol Exp Ther 2008; 325(1): 146-53.
[http://dx.doi.org/10.1124/jpet.107.130526] [PMID: 18199809]
[29]
Jouroukhin Y, Ostritsky R, Assaf Y, Pelled G, Giladi E, Gozes I. NAP (davunetide) modifies disease progression in a mouse model of severe neurodegeneration: protection against impairments in axonal transport. Neurobiol Dis 2013; 56: 79-94.
[http://dx.doi.org/10.1016/j.nbd.2013.04.012] [PMID: 23631872]
[30]
Beyer CF, Zhang N, Hernandez R, et al. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res 2008; 68(7): 2292-300.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1420] [PMID: 18381436]
[31]
Kovalevich J, Cornec AS, Yao Y, et al. Characterization of brain-penetrant pyrimidine-containing molecules with differential microtubule-stabilizing activities developed as potential therapeutic agents for Alzheimer’s disease and related tauopathies. J Pharmacol Exp Ther 2016; 357(2): 432-50.
[http://dx.doi.org/10.1124/jpet.115.231175] [PMID: 26980057]
[32]
Schlachetzki JC, Saliba SW, Oliveira AC. Studying neurodegenerative diseases in culture models. Br J Psychiatry 2013; 35(Suppl. 2): S92-S100.
[http://dx.doi.org/10.1590/1516-4446-2013-1159] [PMID: 24271231]
[33]
Das V, Miller JH. Microtubule stabilization by peloruside A and paclitaxel rescues degenerating neurons from okadaic acid-induced tau phosphorylation. Eur J Neurosci 2012; 35(11): 1705-17.
[http://dx.doi.org/10.1111/j.1460-9568.2012.08084.x] [PMID: 22594877]
[34]
Das V, Sim DA, Miller JH. Effect of taxoid and nontaxoid site microtubule-stabilizing agents on axonal transport of mitochondria in untransfected and ECFP-htau40-transfected rat cortical neurons in culture. J Neurosci Res 2014; 92(9): 1155-66.
[http://dx.doi.org/10.1002/jnr.23394] [PMID: 24788108]
[35]
Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech 2017; 10(5): 499-502.
[http://dx.doi.org/10.1242/dmm.030205] [PMID: 28468935]
[36]
Ishihara T, Zhang B, Higuchi M, Yoshiyama Y, Trojanowski JQ, Lee VM. Age-dependent induction of congophilic neurofibrillary tau inclusions in tau transgenic mice. Am J Pathol 2001; 158(2): 555-62.
[http://dx.doi.org/10.1016/S0002-9440(10)63997-1] [PMID: 11159192]
[37]
Ramsden M, Kotilinek L, Forster C, et al. Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J Neurosci 2005; 25(46): 10637-47.
[http://dx.doi.org/10.1523/JNEUROSCI.3279-05.2005] [PMID: 16291936]
[38]
Yoshiyama Y, Higuchi M, Zhang B, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 2007; 53(3): 337-51.
[http://dx.doi.org/10.1016/j.neuron.2007.01.010] [PMID: 17270732]
[39]
Oddo S, Caccamo A, Shepherd JD, et al. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003; 39(3): 409-21.
[http://dx.doi.org/10.1016/S0896-6273(03)00434-3] [PMID: 12895417]
[40]
He Z, McBride JD, Xu H, et al. Transmission of tauopathy strains is independent of their isoform composition. Nat Commun 2020; 11(1): 7.
[http://dx.doi.org/10.1038/s41467-019-13787-x] [PMID: 31911587]
[41]
Strey CW, Spellman D, Stieber A, et al. Dysregulation of stathmin, a microtubule-destabilizing protein, and up-regulation of Hsp25, Hsp27, and the antioxidant peroxiredoxin 6 in a mouse model of familial amyotrophic lateral sclerosis. Am J Pathol 2004; 165(5): 1701-18.
[http://dx.doi.org/10.1016/S0002-9440(10)63426-8] [PMID: 15509539]
[42]
Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Huntington’s disease is a four-repeat tauopathy with tau nuclear rods. Neuron 2003; 39(6): 889-909.
[http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID: 12971891]
[43]
Brunden KR, Zhang B, Carroll J, et al. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci 2010; 30(41): 13861-6.
[http://dx.doi.org/10.1523/JNEUROSCI.3059-10.2010] [PMID: 20943926]
[44]
Zhang B, Carroll J, Trojanowski JQ, et al. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci 2012; 32(11): 3601-11.
[http://dx.doi.org/10.1523/JNEUROSCI.4922-11.2012] [PMID: 22423084]
[45]
Barten DM, Fanara P, Andorfer C, et al. Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau transgenic mice with low doses of the microtubule-stabilizing agent BMS-241027. J Neurosci 2012; 32(21): 7137-45.
[http://dx.doi.org/10.1523/JNEUROSCI.0188-12.2012] [PMID: 22623658]
[46]
Ruschel J, Hellal F, Flynn KC, et al. Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science 2015; 348(6232): 347-52.
[http://dx.doi.org/10.1126/science.aaa2958] [PMID: 25765066]
[47]
Makani V, Zhang B, Han H, et al. Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in the PS19 tau transgenic mouse model of tauopathy. Acta Neuropathol Commun 2016; 4(1): 106.
[http://dx.doi.org/10.1186/s40478-016-0378-4] [PMID: 27687527]
[48]
Brunden KR, Gardner NM, James MJ, et al. MT-Stabilizer, dictyostatin, exhibits prolonged brain retention and activity: Potential therapeutic implications. ACS Med Chem Lett 2013; 4(9): 886-9.
[http://dx.doi.org/10.1021/ml400233e] [PMID: 24900764]
[49]
Gozes I, Divinski I. The femtomolar-acting NAP interacts with microtubules: Novel aspects of astrocyte protection. J Alzheimers Dis 2004; 6(6)(Suppl.): S37-41.
[PMID: 15665412]
[50]
Matsuoka Y, Gray AJ, Hirata-Fukae C, et al. Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer’s disease at early pathological stage. J Mol Neurosci 2007; 31(2): 165-70.
[PMID: 17478890]
[51]
Zhang N, Ayral-Kaloustian S, Nguyen T, et al. Synthesis and SAR of [1,2,4]triazolo[1,5-a]pyrimidines, a class of anticancer agents with a unique mechanism of tubulin inhibition. J Med Chem 2007; 50(2): 319-27.
[http://dx.doi.org/10.1021/jm060717i] [PMID: 17228873]
[52]
Lou K, Yao Y, Hoye AT, et al. Brain-penetrant, orally bioavailable microtubule-stabilizing small molecules are potential candidate therapeutics for Alzheimer’s disease and related tauopathies. J Med Chem 2014; 57(14): 6116-27.
[http://dx.doi.org/10.1021/jm5005623] [PMID: 24992153]
[53]
Cornec AS, James MJ, Kovalevich J, et al. Pharmacokinetic, pharmacodynamic and metabolic characterization of a brain retentive microtubule (MT)-stabilizing triazolopyrimidine. Bioorg Med Chem Lett 2015; 25(21): 4980-2.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.002] [PMID: 25819095]
[54]
Zhang B, Yao Y, Cornec AS, et al. A brain-penetrant triazolopyrimidine enhances microtubule-stability, reduces axonal dysfunction and decreases tau pathology in a mouse tauopathy model. Mol Neurodegener 2018; 13(1): 59. a
[http://dx.doi.org/10.1186/s13024-018-0291-3] [PMID: 30404654]
[55]
Clark JA, Blizzard CA, Breslin MC, et al. Epothilone D accelerates disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 2018; 44(6): 590-605.
[http://dx.doi.org/10.1111/nan.12473] [PMID: 29380402]
[56]
Pellegrini L, Wetzel A, Grannó S, Heaton G, Harvey K. Back to the tubule: microtubule dynamics in Parkinson’s disease. Cell Mol Life Sci 2017; 74(3): 409-34.
[http://dx.doi.org/10.1007/s00018-016-2351-6] [PMID: 27600680]
[57]
Zhang X, Gao F, Wang D, et al. Tau pathology in Parkinson’s disease. Front Neurol 2018; 9: 809. b
[http://dx.doi.org/10.3389/fneur.2018.00809] [PMID: 30333786 ]
[58]
Henderson MX, Sengupta M, Trojanowski JQ, Lee VMY. Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease. Acta Neuropathol Commun 2019; 7(1): 183.
[http://dx.doi.org/10.1186/s40478-019-0836-x] [PMID: 31733655]
[59]
Fernández-Nogales M, Cabrera JR, Santos-Galindo M, et al. Huntington’s disease is a four-repeat tauopathy with tau nuclear rods. Nat Med 2014; 20(8): 881-5.
[http://dx.doi.org/10.1038/nm.3617] [PMID: 25038828]
[60]
Gratuze M, Cisbani G, Cicchetti F, Planel E. Is Huntington’s disease a tauopathy? Brain 2016; 139(Pt. 4): 1014-25.
[http://dx.doi.org/10.1093/brain/aww021] [PMID: 26969684]
[61]
Magnani E, Fan J, Gasparini L, et al. Interaction of tau protein with the dynactin complex. EMBO J 2007; 26(21): 4546-54.
[http://dx.doi.org/10.1038/sj.emboj.7601878] [PMID: 17932487]
[62]
Cartelli D, Casagrande F, Busceti CL, et al. Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer epothilone D is neuroprotective. Sci Rep 2013; 3: 1837.
[http://dx.doi.org/10.1038/srep01837] [PMID: 23670541]
[63]
Yu Z, Yang L, Yang Y, et al. Epothilone B benefits nigral dopaminergic neurons by attenuating microglia activation in the 6-hydroxydopamine lesion mouse model of Parkinson’s disease. Front Cell Neurosci 2018; 12: 324.
[http://dx.doi.org/10.3389/fncel.2018.00324] [PMID: 30323743]
[64]
Behrouzi R, Liu X, Wu D, et al. Pathological tau deposition in Motor Neurone Disease and frontotemporal lobar degeneration associated with TDP-43 proteinopathy. Acta Neuropathol Commun 2016; 4: 33.
[http://dx.doi.org/10.1186/s40478-016-0301-z] [PMID: 27036121]
[65]
Cross DJ, Meabon JS, Cline MM, et al. Paclitaxel reduces brain injury from repeated head trauma in mice. J Alzheimers Dis 2019; 67(3): 859-74.
[http://dx.doi.org/10.3233/JAD-180871] [PMID: 30664506]
[66]
Fan Y, Wali G, Sutharsan R, et al. Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia. Biol Open 2014; 3(6): 494-502.
[http://dx.doi.org/10.1242/bio.20147641] [PMID: 24857849]
[67]
Pramanik S, Sulistio YA, Heese K. Neurotrophin signaling and stem cells-implications for neurodegenerative diseases and stem cell therapy. Mol Neurobiol 2017; 54(9): 7401-59.
[http://dx.doi.org/10.1007/s12035-016-0214-7] [PMID: 27815842]
[68]
Mertens J, Stüber K, Poppe D, et al. Embryonic stem cell-based modeling of tau pathology in human neurons. Am J Pathol 2013; 182(5): 1769-79.
[http://dx.doi.org/10.1016/j.ajpath.2013.01.043] [PMID: 23499461]
[69]
Paonessa F, Evans LD, Solanki R, et al. Microtubules deform the nuclear membrane and disrupt nucleocytoplasmic transport in tau-mediated frontotemporal dementia. Cell Rep 2019; 26(3): 582-593.e5.
[http://dx.doi.org/10.1016/j.celrep.2018.12.085] [PMID: 30650353]
[70]
Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc 2014; 9(10): 2329-40.
[http://dx.doi.org/10.1038/nprot.2014.158] [PMID: 25188634]
[71]
Gonzalez C, Armijo E, Bravo-Alegria J, Becerra-Calixto A, Mays CE, Soto C. Modeling amyloid beta and tau pathology in human cerebral organoids. Mol Psychiatry 2018; 23(12): 2363-74.
[http://dx.doi.org/10.1038/s41380-018-0229-8] [PMID: 30171212]
[72]
Sposito T, Preza E, Mahoney CJ, et al. Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT. Hum Mol Genet 2015; 24(18): 5260-9.
[http://dx.doi.org/10.1093/hmg/ddv246] [PMID: 26136155]
[73]
Alonso AD, Cohen LS, Corbo C, et al. Hyperphosphorylation of tau associates with changes in its function beyond microtubule stability. Front Cell Neurosci 2018; 12: 338.
[http://dx.doi.org/10.3389/fncel.2018.00338] [PMID: 30356756]
[74]
Pérez MJ, Jara C, Quintanilla RA. Contribution of tau pathology to mitochondrial impairment in neurodegeneration. Front Neurosci 2018; 12: 441.
[http://dx.doi.org/10.3389/fnins.2018.00441] [PMID: 30026680]
[75]
Silva DF, Esteves AR, Oliveira CR, Cardoso SM. Mitochondrial metabolism power SIRT2-dependent deficient traffic causing Alzheimer’s-disease related pathology. Mol Neurobiol 2017; 54(6): 4021-40.
[http://dx.doi.org/10.1007/s12035-016-9951-x] [PMID: 27311773]
[76]
Tse KH, Herrup K. Re-imagining Alzheimer’s disease - the diminishing importance of amyloid and a glimpse of what lies ahead. J Neurochem 2017; 143(4): 432-44.
[http://dx.doi.org/10.1111/jnc.14079] [PMID: 28547865]
[77]
Hahn I, Voelzmann A, Liew YT, Costa-Gomes B, Prokop A. The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology. Neural Dev 2019; 14(1): 11.
[http://dx.doi.org/10.1186/s13064-019-0134-0] [PMID: 31706327]
[78]
Coles CH, Bradke F. Coordinating neuronal actin-microtubule dynamics. Curr Biol 2015; 25(15): R677-91.
[http://dx.doi.org/10.1016/j.cub.2015.06.020] [PMID: 26241148]
[79]
Kellogg EH, Hejab NMA, Howes S, et al. Insights into the distinct mechanisms of action of taxane and non-taxane microtubule stabilizers from cryo-EM structures. J Mol Biol 2017; 429(5): 633-46.
[http://dx.doi.org/10.1016/j.jmb.2017.01.001] [PMID: 28104363]
[80]
Mohan R, John A. Microtubule-associated proteins as direct crosslinkers of actin filaments and microtubules. IUBMB Life 2015; 67(6): 395-403.
[http://dx.doi.org/10.1002/iub.1384] [PMID: 26104829]
[81]
Malamut R, Wang J-S, Savant I, et al. A randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of a microtubule stabilizer (BMS-241027) in healthy females. Alzheimers Dement 2013; 9(4)(Suppl.): 668-P9.
[http://dx.doi.org/10.1016/j.jalz.2013.05.1378]
[82]
Tsai RM, Miller Z, Koestler M, et al. Reactions to multiple ascending doses of the microtubule stabilizer TPI-287 in patients with Alzheimer disease, progressive supranuclear palsy, and corticobasal syndrome: A randomized clinical trial. JAMA Neurol 2020; 77(2): 215-24.
[http://dx.doi.org/10.1001/jamaneurol.2019.3812] [PMID: 31710340]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 35
Year: 2020
Published on: 15 October, 2020
Page: [4362 - 4372]
Pages: 11
DOI: 10.2174/1381612826666200621171302
Price: $65

Article Metrics

PDF: 25
HTML: 2
EPUB: 1
PRC: 1