Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Transcriptional Dysregulation in Huntington’s Disease: The Role in Pathogenesis and Potency for Pharmacological Targeting

Author(s): Aleksandra Pogoda, Natalia Chmielewska*, Piotr Maciejak and Janusz Szyndler

Volume 28, Issue 14, 2021

Published on: 05 July, 2020

Page: [2783 - 2806] Pages: 24

DOI: 10.2174/0929867327666200705225821

open access plus


Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the gene that encodes a critical cell regulatory protein, huntingtin (Htt). The expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats causes improper folding of functional proteins and is an initial trigger of pathological changes in the brain. Recent research has indicated that the functional dysregulation of many transcription factors underlies the neurodegenerative processes that accompany HD. These disturbances are caused not only by the loss of wild-type Htt (WT Htt) function but also by the occurrence of abnormalities that result from the action of mutant Htt (mHtt).

In this review, we aim to describe the role of transcription factors that are currently thought to be strongly associated with HD pathogenesis, namely, RE1-silencing transcription factor, also known as neuron-restrictive silencer factor (REST/NRSF), forkhead box proteins (FOXPs), peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1α), heat shock transcription factor 1 (HSF1), and nuclear factor κ light-chain-enhancer of activated B cells (NF- κB). We also take into account the role of these factors in the phenotype of HD as well as potential pharmacological interventions targeting the analyzed proteins. Furthermore, we considered whether molecular manipulation resulting in changes in transcription factor function may have clinical potency for treating HD.

Keywords: Huntington's Disease, transcription factors, transcriptional dysregulation, REST/NRSF, FOXPs, PGC1α, HSF1, NF-κB.

MacDonald, M.E.; Ambrose, C.M.; Duyao, M.P.; Myers, R.H.; Lin, C.; Srinidhi, L.; Barnes, G.; Taylor, S.A.; James, M.; Groot, N.; MacFarlane, H.; Jenkins, B.; Anderson, M.A.; Wexler, N.S.; Gusella, J.S. The Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell, 1993, 72(6), 971-983.
[] [PMID: 8458085]
Rubinsztein, D.C. The molecular pathology of Huntington’s Disease (HD). Curr. Med. Chem. Immunol. Endocr. Metab. Agents, 2003, 3(4), 329-334.
[ ]
Roos, R.A. Huntington’s disease: a clinical review. Orphanet J. Rare Dis., 2010, 5(40), 40.
[] [PMID: 21171977]
Graveland, G.A.; Williams, R.S.; DiFiglia, M. Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington’s disease. Science, 1985, 227(4688), 770-773.
[] [PMID: 3155875]
Vonsattel, J.P.; DiFiglia, M. Huntington disease. J. Neuropathol. Exp. Neurol., 1998, 57(5), 369-384.
[] [PMID: 9596408]
Panegyres, P.K.; Goh, J.G.S. The neurology and natural history of patients with indeterminate CAG repeat length mutations of the Huntington disease gene. J. Neurol. Sci., 2011, 301(1-2), 14-20.
[] [PMID: 21147489]
Luthi-Carter, R.; Cha, J.H. Mechanisms of transcriptional dysregulation in Huntington’s disease. Clin. Neurosci. Res., 2003, 3, 165-177.
Langfelder, P.; Cantle, J.P.; Chatzopoulou, D.; Wang, N.; Gao, F.; Al-Ramahi, I.; Lu, X.H.; Ramos, E.M.; El-Zein, K.; Zhao, Y.; Deverasetty, S.; Tebbe, A.; Schaab, C.; Lavery, D.J.; Howland, D.; Kwak, S.; Botas, J.; Aaronson, J.S.; Rosinski, J.; Coppola, G.; Horvath, S.; Yang, X.W. Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice. Nat. Neurosci., 2016, 19(4), 623-633.
[] [PMID: 26900923]
Ament, S.A.; Pearl, J.R.; Grindeland, A.; St Claire, J.; Earls, J.C.; Kovalenko, M.; Gillis, T.; Mysore, J.; Gusella, J.F.; Lee, J.M.; Kwak, S.; Howland, D.; Lee, M.Y.; Baxter, D.; Scherler, K.; Wang, K.; Geman, D.; Carroll, J.B.; MacDonald, M.E.; Carlson, G.; Wheeler, V.C.; Price, N.D.; Hood, L.E. High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington’s disease CAG knock-in mice across multiple genetic backgrounds. Hum. Mol. Genet., 2017, 26(5), 913-922.
[] [PMID: 28334820]
Tellone, E.; Galtieri, A.; Ficarra, S. Reviewing the biochemical implications of normal and mutated huntingtin in Huntington’s disease. Curr. Med. Chem., 2020, 27(31), 5137-5158.
[] [PMID: 31223078]
Hickey, M.A.; Chesselet, M.F. Apoptosis in Huntington’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2003, 27(2), 255-265.
[] [PMID: 12657365]
Saudou, F.; Humbert, S. The Biology of huntingtin. Neuron, 2016, 89(5), 910-926.
[] [PMID: 26938440]
McClelland, S.; Brennan, G.P.; Dubé, C.; Rajpara, S.; Iyer, S.; Richichi, C.; Bernard, C.; Baram, T.Z. The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes. eLife, 2014, 3, e01267.
[] [PMID: 25117540]
Zuccato, C.; Tartari, M.; Crotti, A.; Goffredo, D.; Valenza, M.; Conti, L.; Cataudella, T.; Leavitt, B.R.; Hayden, M.R.; Timmusk, T.; Rigamonti, D.; Cattaneo, E. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat. Genet., 2003, 35(1), 76-83.
[] [PMID: 12881722]
Dickey, A.S.; Pineda, V.V.; Tsunemi, T.; Liu, P.P.; Miranda, H.C.; Gilmore-Hall, S.K.; Lomas, N.; Sampat, K.R.; Buttgereit, A.; Torres, M.J.M.; Flores, A.L.; Arreola, M.; Arbez, N.; Akimov, S.S.; Gaasterland, T.; Lazarowski, E.R.; Ross, C.A.; Yeo, G.W.; Sopher, B.L.; Magnuson, G.K.; Pinkerton, A.B.; Masliah, E.; La Spada, A.R. PPAR-δ is repressed in Huntington’s disease, is required for normal neuronal function and can be targeted therapeutically. Nat. Med., 2016, 22(1), 37-45.
[] [PMID: 26642438]
Tang, B.; Becanovic, K.; Desplats, P.A.; Spencer, B.; Hill, A.M.; Connolly, C.; Masliah, E.; Leavitt, B.R.; Thomas, E.A. Forkhead box protein p1 is a transcriptional repressor of immune signaling in the CNS: implications for transcriptional dysregulation in Huntington disease. Hum. Mol. Genet., 2012, 21(14), 3097-3111.
[] [PMID: 22492998]
Carter, M.E.; Brunet, A. FOXO transcription factors. Curr. Biol., 2007, 17(4), R113-R114.
[] [PMID: 17307039]
Hachigian, L.J.; Carmona, V.; Fenster, R.J.; Kulicke, R.; Heilbut, A.; Sittler, A.; Pereira de Almeida, L.; Mesirov, J.P.; Gao, F.; Kolaczyk, E.D.; Heiman, M. Control of Huntington’s disease-associated phenotypes by the striatum-enriched transcription factor Foxp2. Cell Rep., 2017, 21(10), 2688-2695.
[] [PMID: 29212017]
Louis Sam Titus, A.S.C.; Yusuff, T.; Cassar, M.; Thomas, E.; Kretzschmar, D.; D’Mello, S.R. Reduced expression of Foxp1 as a contributing factor in Huntington’s Disease. J. Neurosci., 2017, 37(27), 6575-6587.
[] [PMID: 28550168]
Li, J.Y.; Popovic, N.; Brundin, P. The use of the R6 transgenic mouse models of Huntington’s disease in attempts to develop novel therapeutic strategies. NeuroRx, 2005, 2(3), 447-464.
[] [PMID: 16389308]
Becker, E.B.; Bonni, A. Cell cycle regulation of neuronal apoptosis in development and disease. Prog. Neurobiol., 2004, 72(1), 1-25.
[] [PMID: 15019174]
Greene, L.A.; Liu, D.X.; Troy, C.M.; Biswas, S.C. Cell cycle molecules define a pathway required for neuron death in development and disease. Biochim. Biophys. Acta, 2007, 1772(4), 392-401.
[] [PMID: 17229557]
Takahashi, K.; Liu, F.C.; Hirokawa, K.; Takahashi, H. Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum. J. Neurosci. Res., 2003, 73(1), 61-72.
[] [PMID: 12815709]
Lee, C.Y.; Cantle, J.P.; Yang, X.W. Genetic manipulations of mutant huntingtin in mice: new insights into Huntington’s disease pathogenesis. FEBS J., 2013, 280(18), 4382-4394.
[] [PMID: 23829302]
Merrill, M.A.; Malik, Z.; Akyol, Z.; Bartos, J.A.; Leonard, A.S.; Hudmon, A.; Shea, M.A.; Hell, J.W. Displacement of alpha-actinin from the NMDA receptor NR1 C0 domain By Ca2+/calmodulin promotes CaMKII binding. Biochemistry, 2007, 46(29), 8485-8497.
[] [PMID: 17602661]
Zhang, L.; Zhao, Y. The regulation of Foxp3 expression in regulatory CD4(+)CD25(+)T cells: multiple pathways on the road. J. Cell. Physiol., 2007, 211(3), 590-597.
[] [PMID: 17311282]
Takenaka, M.; Seki, N.; Toh, U.; Hattori, S.; Kawahara, A.; Yamaguchi, T.; Koura, K.; Takahashi, R.; Otsuka, H.; Takahashi, H.; Iwakuma, N.; Nakagawa, S.; Fujii, T.; Sasada, T.; Yamaguchi, R.; Yano, H.; Shirouzu, K.; Kage, M. FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Mol. Clin. Oncol., 2013, 1(4), 625-632.
[] [PMID: 24649219]
Bennett, C.L.; Christie, J.; Ramsdell, F.; Brunkow, M.E.; Ferguson, P.J.; Whitesell, L.; Kelly, T.E.; Saulsbury, F.T.; Chance, P.F.; Ochs, H.D. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet., 2001, 27(1), 20-21.
[] [PMID: 11137993]
Takahashi, K.; Liu, F.C.; Hirokawa, K.; Takahashi, H. Expression of Foxp4 in the developing and adult rat forebrain. J. Neurosci. Res., 2008, 86(14), 3106-3116.
[] [PMID: 18561326]
Tam, W.Y.; Leung, C.K.; Tong, K.K.; Kwan, K.M. Foxp4 is essential in maintenance of Purkinje cell dendritic arborization in the mouse cerebellum. Neuroscience, 2011, 172(172), 562-571.
[] [PMID: 20951773]
Beal, M.F.; Hyman, B.T.; Koroshetz, W. Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci., 1993, 16(4), 125-131.
[] [PMID: 7682343]
Aziz, N.A.; van der Burg, J.M.M.; Landwehrmeyer, G.B.; Brundin, P.; Stijnen, T.; Roos, R.A. EHDI Study Group. Weight loss in Huntington disease increases with higher CAG repeat number. Neurology, 2008, 71(19), 1506-1513.
[] [PMID: 18981372]
Lowell, B.B.; Spiegelman, B.M. Towards a molecular understanding of adaptive thermogenesis. Nature, 2000, 404(6778), 652-660.
[] [PMID: 10766252]
Seong, I.S.; Ivanova, E.; Lee, J.M.; Choo, Y.S.; Fossale, E.; Anderson, M.; Gusella, J.F.; Laramie, J.M.; Myers, R.H.; Lesort, M.; MacDonald, M.E.H.D.H.D. CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Hum. Mol. Genet., 2005, 14(19), 2871-2880.
[] [PMID: 16115812]
Puigserver, P.; Wu, Z.; Park, C.W.; Graves, R.; Wright, M.; Spiegelman, B.M. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998, 92(6), 829-839.
[] [PMID: 9529258]
St-Pierre, J.; Drori, S.; Uldry, M.; Silvaggi, J.M.; Rhee, J.; Jäger, S.; Handschin, C.; Zheng, K.; Lin, J.; Yang, W.; Simon, D.K.; Bachoo, R.; Spiegelman, B.M. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell, 2006, 127(2), 397-408.
[] [PMID: 17055439]
Leone, T.C.; Lehman, J.J.; Finck, B.N.; Schaeffer, P.J.; Wende, A.R.; Boudina, S.; Courtois, M.; Wozniak, D.F.; Sambandam, N.; Bernal-Mizrachi, C.; Chen, Z.; Holloszy, J.O.; Medeiros, D.M.; Schmidt, R.E.; Saffitz, J.E.; Abel, E.D.; Semenkovich, C.F.; Kelly, D.P. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol., 2005, 3(4), e101.
[] [PMID: 15760270]
Weydt, P.; Pineda, V.V.; Torrence, A.E.; Libby, R.T.; Satterfield, T.F.; Lazarowski, E.R.; Gilbert, M.L.; Morton, G.J.; Bammler, T.K.; Strand, A.D.; Cui, L.; Beyer, R.P.; Easley, C.N.; Smith, A.C.; Krainc, D.; Luquet, S.; Sweet, I.R.; Schwartz, M.W.; La Spada, A.R. Thermoregulatory and metabolic defects in Huntington’s disease transgenic mice implicate PGC-1alpha in Huntington’s disease neurodegeneration. Cell Metab., 2006, 4(5), 349-362.
[] [PMID: 17055784]
Cui, L.; Jeong, H.; Borovecki, F.; Parkhurst, C.N.; Tanese, N.; Krainc, D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell, 2006, 127(1), 59-69.
[] [PMID: 17018277]
Lin, J.; Wu, P.H.; Tarr, P.T.; Lindenberg, K.S.; St-Pierre, J.; Zhang, C.Y.; Mootha, V.K.; Jäger, S.; Vianna, C.R.; Reznick, R.M.; Cui, L.; Manieri, M.; Donovan, M.X.; Wu, Z.; Cooper, M.P.; Fan, M.C.; Rohas, L.M.; Zavacki, A.M.; Cinti, S.; Shulman, G.I.; Lowell, B.B.; Krainc, D.; Spiegelman, B.M. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell, 2004, 119(1), 121-135.
[] [PMID: 15454086]
Wiggs, M.P. Can endurance exercise preconditioning prevention disuse muscle atrophy? Front. Physiol., 2015, 6(6), 63.
[] [PMID: 25814955]
Jesse, S.; Bayer, H.; Alupei, M.C.; Zügel, M.; Mulaw, M.; Tuorto, F.; Malmsheimer, S.; Singh, K.; Steinacker, J.; Schumann, U.; Ludolph, A.C.; Scharffetter-Kochanek, K.; Witting, A.; Weydt, P.; Iben, S. Ribosomal transcription is regulated by PGC-1alpha and disturbed in Huntington’s disease. Sci. Rep., 2017, 7(1), 8513.
[] [PMID: 28819135]
Tsunemi, T.; Ashe, T.D.; Morrison, B.E.; Soriano, K.R.; Au, J.; Roque, R.A.; Lazarowski, E.R.; Damian, V.A.; Masliah, E.; La Spada, A.R. PGC-1α rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci. Transl. Med., 2012, 4(142), 142ra97.
[] [PMID: 22786682]
Neueder, A.; Achilli, F.; Moussaoui, S.; Bates, G.P. Novel isoforms of heat shock transcription factor 1, HSF1γα and HSF1γβ, regulate chaperone protein gene transcription. J. Biol. Chem., 2014, 289(29), 19894-19906.
[] [PMID: 24855652]
Neef, D.W.; Jaeger, A.M.; Thiele, D.J. Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat. Rev. Drug Discov., 2011, 10(12), 930-944.
[] [PMID: 22129991]
Watanabe, Y.; Tsujimura, A.; Taguchi, K.; Tanaka, M. HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis. Autophagy, 2017, 13(1), 133-148.
[] [PMID: 27846364]
Riva, L.; Koeva, M.; Yildirim, F.; Pirhaji, L.; Dinesh, D.; Mazor, T.; Duennwald, M.L.; Fraenkel, E. Poly-glutamine expanded huntingtin dramatically alters the genome wide binding of HSF1. J. Huntingtons Dis., 2012, 1(1), 33-45.
[] [PMID: 23293686]
Gomez-Pastor, R.; Burchfiel, E.T.; Neef, D.W.; Jaeger, A.M.; Cabiscol, E.; McKinstry, S.U.; Doss, A.; Aballay, A.; Lo, D.C.; Akimov, S.S.; Ross, C.A.; Eroglu, C.; Thiele, D.J. Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington’s disease. Nat. Commun., 2017, 8(8), 14405.
[] [PMID: 28194040]
DiProspero, N.A.; Chen, E.Y.; Charles, V.; Plomann, M.; Kordower, J.H.; Tagle, D.A. Early changes in Huntington’s disease patient brains involve alterations in cytoskeletal and synaptic elements. J. Neurocytol., 2004, 33(5), 517-533.
[] [PMID: 15906159]
Kaltenbach, L.S.; Romero, E.; Becklin, R.R.; Chettier, R.; Bell, R.; Phansalkar, A.; Strand, A.; Torcassi, C.; Savage, J.; Hurlburt, A.; Cha, G.H.; Ukani, L.; Chepanoske, C.L.; Zhen, Y.; Sahasrabudhe, S.; Olson, J.; Kurschner, C.; Ellerby, L.M.; Peltier, J.M.; Botas, J.; Hughes, R.E. Huntingtin interacting proteins are genetic modifiers of neurodegeneration. PLoS Genet., 2007, 3(5), e82.
[] [PMID: 17500595]
Gauthier, L.R.; Charrin, B.C.; Borrell-Pagès, M.; Dompierre, J.P.; Rangone, H.; Cordelières, F.P.; De Mey, J.; MacDonald, M.E.; Lessmann, V.; Humbert, S.; Saudou, F. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell, 2004, 118(1), 127-138.
[] [PMID: 15242649]
Caviston, J.P.; Ross, J.L.; Antony, S.M.; Tokito, M.; Holzbaur, E.L. Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc. Natl. Acad. Sci. USA, 2007, 104(24), 10045-10050.
[] [PMID: 17548833]
Munsie, L.; Caron, N.; Atwal, R.S.; Marsden, I.; Wild, E.J.; Bamburg, J.R.; Tabrizi, S.J.; Truant, R. Mutant huntingtin causes defective actin remodeling during stress: defining a new role for transglutaminase 2 in neurodegenerative disease. Hum. Mol. Genet., 2011, 20(10), 1937-1951.
[] [PMID: 21355047]
Fuchs, M.; Poirier, D.J.; Seguin, S.J.; Lambert, H.; Carra, S.; Charette, S.J.; Landry, J. Identification of the key structural motifs involved in HspB8/HspB6-Bag3 interaction. Biochem. J., 2009, 425(1), 245-255.
[] [PMID: 19845507]
Gomez-Pastor, R.; Burchfiel, E.T.; Neef, D.W.; Jaeger, A.M.; Cabiscol, E.; McKinstry, S.U.; Doss, A.; Aballay, A.; Lo, D.C.; Akimov, S.S.; Ross, C.A.; Eroglu, C.; Thiele, D.J. Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington’s disease. Nat. Commun., 2017, 13(8), 14405.
[ ] [PMID: 28194040]
Intihar, T.A.; Martinez, E.A.; Gomez-Pastor, R. Mitochondrial dysfunction in Huntington’s disease; interplay between HSF1, p53 and PGC-1α transcription factors. Front. Cell. Neurosci., 2019, 13, 103.
[] [PMID: 30941017]
Zeron, M.M.; Hansson, O.; Chen, N.; Wellington, C.L.; Leavitt, B.R.; Brundin, P.; Hayden, M.R.; Raymond, L.A. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington’s disease. Neuron, 2002, 33(6), 849-860.
[] [PMID: 11906693]
Kolodziejczyk, K.; Raymond, L.A. Differential changes in thalamic and cortical excitatory synapses onto striatal spiny projection neurons in a Huntington disease mouse model. Neurobiol. Dis., 2016, 86, 62-74.
[] [PMID: 26621114]
Schoenherr, C.J.; Anderson, D.J. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science, 1995, 267(5202), 1360-1363.
[] [PMID: 7871435]
Bruce, A.W.; Donaldson, I.J.; Wood, I.C.; Yerbury, S.A.; Sadowski, M.I.; Chapman, M.; Göttgens, B.; Buckley, N.J. Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes. Proc. Natl. Acad. Sci. USA, 2004, 101(28), 10458-10463.
[] [PMID: 15240883]
Roopra, A.; Sharling, L.; Wood, I.C.; Briggs, T.; Bachfischer, U.; Paquette, A.J.; Buckley, N.J. Transcriptional repression by neuron-restrictive silencer factor is mediated via the Sin3-histone deacetylase complex. Mol. Cell. Biol., 2000, 20(6), 2147-2157.
[] [PMID: 10688661]
Glozak, M.A.; Sengupta, N.; Zhang, X.; Seto, E. Acetylation and deacetylation of non-histone proteins. Gene, 2005, 363, 15-23.
[] [PMID: 16289629]
Andrés, M.E.; Burger, C.; Peral-Rubio, M.J.; Battaglioli, E.; Anderson, M.E.; Grimes, J.; Dallman, J.; Ballas, N.; Mandel, G. CoREST: a functional corepressor required for regulation of neural-specific gene expression. Proc. Natl. Acad. Sci. USA, 1999, 96(17), 9873-9878.
[] [PMID: 10449787]
Roopra, A.; Qazi, R.; Schoenike, B.; Daley, T.J.; Morrison, J.F. Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes. Mol. Cell, 2004, 14(6), 727-738.
[] [PMID: 15200951]
Baquet, Z.C.; Gorski, J.A.; Jones, K.R.; Jones, K.R. Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor. J. Neurosci., 2004, 24(17), 4250-4258.
[] [PMID: 15115821]
Rodenas-Ruano, A.; Chávez, A.E.; Cossio, M.J.; Castillo, P.E.; Zukin, R.S. REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors. Nat. Neurosci., 2012, 15(10), 1382-1390.
[] [PMID: 22960932]
Chmielewska, N.; Wawer, A.; Maciejak, P.; Turzyńska, D.; Sobolewska, A.; Skórzewska, A.; Osuch, B.; Płaźnik, A.; Szyndler, J. The role of REST/NRSF, TrkB and BDNF in neurobiological mechanisms of different susceptibility to seizure in a PTZ model of epilepsy. Brain Res. Bull., 2020, 158, 108-115.
[] [PMID: 32151715]
Formisano, L.; Noh, K.M.; Miyawaki, T.; Mashiko, T.; Bennett, M.V.; Zukin, R.S. Ischemic insults promote epigenetic reprogramming of mu opioid receptor expression in hippocampal neurons. Proc. Natl. Acad. Sci. USA, 2007, 104(10), 4170-4175.
[] [PMID: 17360495]
Chmielewska, N.; Szyndler, J.; Maciejak, P.; Płaźnik, A. Epigenetic mechanisms of stress and depression. Psychiatr. Pol., 2019, 53(6), 1413-1428.
[] [PMID: 32017826]
Buckley, N.J.; Johnson, R.; Zuccato, C.; Bithell, A.; Cattaneo, E. The role of REST in transcriptional and epigenetic dysregulation in Huntington’s disease. Neurobiol. Dis., 2010, 39(1), 28-39.
[] [PMID: 20170730]
Zuccato, C.; Belyaev, N.; Conforti, P.; Ooi, L.; Tartari, M.; Papadimou, E.; MacDonald, M.; Fossale, E.; Zeitlin, S.; Buckley, N.; Cattaneo, E. Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington’s disease. J. Neurosci., 2007, 27(26), 6972-6983.
[] [PMID: 17596446]
Soldati, C.; Bithell, A.; Conforti, P.; Cattaneo, E.; Buckley, N.J. Rescue of gene expression by modified REST decoy oligonucleotides in a cellular model of Huntington’s disease. J. Neurochem., 2011, 116(3), 415-425.
[] [PMID: 21105876]
Wong, P.T.; McGeer, P.L.; Rossor, M.; McGeer, E.G. Ornithine aminotransferase in Huntington’s disease. Brain Res., 1982, 231(2), 466-471.
[] [PMID: 6459816]
Guiretti, D.; Sempere, A.; Lopez-Atalaya, J.P.; Ferrer-Montiel, A.; Barco, A.; Valor, L.M. Specific promoter deacetylation of histone H3 is conserved across mouse models of Huntington’s disease in the absence of bulk changes. Neurobiol. Dis., 2016, 89, 190-201.
[] [PMID: 26851501]
Ferrante, R.J.; Ryu, H.; Kubilus, J.K.; D’Mello, S.; Sugars, K.L.; Lee, J.; Lu, P.; Smith, K.; Browne, S.; Beal, M.F.; Kristal, B.S.; Stavrovskaya, I.G.; Hewett, S.; Rubinsztein, D.C.; Langley, B.; Ratan, R.R. Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington’s disease. J. Neurosci., 2004, 24(46), 10335-10342.
[] [PMID: 15548647]
Gardian, G.; Browne, S.E.; Choi, D.K.; Klivenyi, P.; Gregorio, J.; Kubilus, J.K.; Ryu, H.; Langley, B.; Ratan, R.R.; Ferrante, R.J.; Beal, M.F. Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington’s disease. J. Biol. Chem., 2005, 280(1), 556-563.
[] [PMID: 15494404]
Tahiliani, M.; Mei, P.; Fang, R.; Leonor, T.; Rutenberg, M.; Shimizu, F.; Li, J.; Rao, A.; Shi, Y. The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature, 2007, 447(7144), 601-605.
[] [PMID: 17468742]
Perkins, N.D. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat. Rev. Mol. Cell Biol., 2007, 8(1), 49-62.
[] [PMID: 17183360]
O’Neill, L.A.; Kaltschmidt, C. NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci., 1997, 20(6), 252-258.
[] [PMID: 9185306]
Meffert, M.K.; Chang, J.M.; Wiltgen, B.J.; Fanselow, M.S.; Baltimore, D. NF-kappa B functions in synaptic signaling and behavior. Nat. Neurosci., 2003, 6(10), 1072-1078.
[] [PMID: 12947408]
Fridmacher, V.; Kaltschmidt, B.; Goudeau, B.; Ndiaye, D.; Rossi, F.M.; Pfeiffer, J.; Kaltschmidt, C.; Israël, A.; Mémet, S. Forebrain-specific neuronal inhibition of nuclear factor-kappaB activity leads to loss of neuroprotection. J. Neurosci., 2003, 23(28), 9403-9408.
[] [PMID: 14561868]
Wellmann, H.; Kaltschmidt, B.; Kaltschmidt, C. Retrograde transport of transcription factor NF-kappa B in living neurons. J. Biol. Chem., 2001, 276(15), 11821-11829.
[] [PMID: 11096106]
Jordan, B.A.; Kreutz, M.R. Nucleocytoplasmic protein shuttling: the direct route in synapse-to-nucleus signaling. Trends Neurosci., 2009, 32(7), 392-401.
[] [PMID: 19524307]
Maggirwar, S.B.; Sarmiere, P.D.; Dewhurst, S.; Freeman, R.S. Nerve growth factor-dependent activation of NF-kappaB contributes to survival of sympathetic neurons. J. Neurosci., 1998, 18(24), 10356-10365.
[] [PMID: 9852573]
Albensi, B.C.; Mattson, M.P. Evidence for the involvement of TNF and NF-kappaB in hippocampal synaptic plasticity. Synapse, 2000, 35(2), 151-159.
[<151:AID-SYN8>3.0.CO;2-P] [PMID: 10611641]
Mikenberg, I.; Widera, D.; Kaus, A.; Kaltschmidt, B.; Kaltschmidt, C. Transcription factor NF-kappaB is transported to the nucleus via cytoplasmic dynein/dynactin motor complex in hippocampal neurons. PLoS One, 2007, 2(7), e589.
[] [PMID: 17622342]
Marcora, E.; Kennedy, M.B. The Huntington’s disease mutation impairs Huntingtin’s role in the transport of NF-κB from the synapse to the nucleus. Hum. Mol. Genet., 2010, 19(22), 4373-4384.
[] [PMID: 20739295]
Colin, E.; Zala, D.; Liot, G.; Rangone, H.; Borrell-Pagès, M.; Li, X.J.; Saudou, F.; Humbert, S. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J., 2008, 27(15), 2124-2134.
[] [PMID: 18615096]
Trushina, E.; Dyer, R.B.; Badger, J.D., II; Ure, D.; Eide, L.; Tran, D.D.; Vrieze, B.T.; Legendre-Guillemin, V.; McPherson, P.S.; Mandavilli, B.S.; Van Houten, B.; Zeitlin, S.; McNiven, M.; Aebersold, R.; Hayden, M.; Parisi, J.E.; Seeberg, E.; Dragatsis, I.; Doyle, K.; Bender, A.; Chacko, C.; McMurray, C.T. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell. Biol., 2004, 24(18), 8195-8209.
[] [PMID: 15340079]
Mattson, M.P.; Meffert, M.K. Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Cell Death Differ., 2006, 13(5), 852-860.
[] [PMID: 16397579]
Träger, U.; Andre, R.; Lahiri, N.; Magnusson-Lind, A.; Andreas, A.; Grueninger, S.; McKinnon, Ch.; Sirinathsinghji, E.; Kahlon, S.; Pfister, E.L.; Moser, R.; Hummerich, H.; Antoniou, M.; Bates, G.P.; Luthi-Carter, R.; Lowdell, M.W.; Björkqvist, M.; Ostroff, G.R.; Aronin, N.; Tabrizi, S.J. HTT-lowering reverses Huntington’s disease immune dysfunction caused by NFkB pathway dysregulation. Brain, 2014, 137(3), 819-833.
[] [PMID: 24459107]
Politis, M.; Pavese, N.; Tai, Y.F.; Kiferle, L.; Mason, S.L.; Brooks, D.J.; Tabrizi, S.J.; Barker, R.A.; Piccini, P. Microglial activation in regions related to cognitive function predicts disease onset in Huntington’s disease: a multimodal imaging study. Hum. Brain Mapp., 2011, 32(2), 258-270.
[] [PMID: 21229614]
Beaumont, V.; Zhong, S.; Lin, H.; Xu, W.; Bradaia, A.; Steidl, E.; Gleyzes, M.; Wadel, K.; Buisson, B.; Padovan-Neto, F.E.; Chakroborty, S.; Ward, K.M.; Harms, J.F.; Beltran, J.; Kwan, M.; Ghavami, A.; Häggkvist, J.; Tóth, M.; Halldin, C.; Varrone, A.; Schaab, C.; Dybowski, J.N.; Elschenbroich, S.; Lehtimäki, K.; Heikkinen, T.; Park, L.; Rosinski, J.; Mrzljak, L.; Lavery, D.; West, A.R.; Schmidt, C.J.; Zaleska, M.M.; Munoz-Sanjuan, I. Phosphodiesterase 10A inhibition improves cortico-basal ganglia function in Huntington’s disease models. Neuron, 2016, 92(6), 1220-1237.
[] [PMID: 27916455]
Rigamonti, D.; Mutti, C.; Zuccato, C.; Cattaneo, E.; Contini, A. Turning REST/NRSF dysfunction in Huntington’s disease into a pharmaceutical target. Curr. Pharm. Des., 2009, 15(34), 3958-3967.
[] [PMID: 19751206]
Fuller, G.N.; Su, X.; Price, R.E.; Cohen, Z.R.; Lang, F.F.; Sawaya, R.; Majumder, S. Many human medulloblastoma tumors overexpress repressor element-1 silencing transcription (REST)/neuron-restrictive silencer factor, which can be functionally countered by REST-VP16. Mol. Cancer Ther., 2005, 4(3), 343-349.
[ ] [PMID: 15767543]
Saw, P.E.; Song, E.W. siRNA therapeutics: a clinical reality. Sci. China Life Sci., 2020, 63(4), 485-500.
[] [PMID: 31054052]
Park, I.K.; Lasiene, J.; Chou, S.H.; Horner, P.J.; Pun, S.H. Neuron-specific delivery of nucleic acids mediated by Tet1-modified poly(ethylenimine). J. Gene Med., 2007, 9(8), 691-702.
[] [PMID: 17582226]
Vagner, T.; Young, D.; Mouravlev, A. Nucleic acid-based therapy approaches for Huntington’s disease. Neurol. Res. Int., 2012, 2012, 358370.
[] [PMID: 22288011]
Soldati, C.; Bithell, A.; Johnston, C.; Wong, K.Y.; Stanton, L.W.; Buckley, N.J. Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington’s disease. J. Neurochem., 2013, 124(3), 418-430.
[] [PMID: 23145961]
Shimojo, M.; Hersh, L.B. REST/NRSF-interacting LIM domain protein, a putative nuclear translocation receptor. Mol. Cell. Biol., 2003, 23(24), 9025-9031.
[] [PMID: 14645515]
Shimojo, M. Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued. J. Biol. Chem., 2008, 283(50), 34880-34886.
[] [PMID: 18922795]
Todd, D.; Gowers, I.; Dowler, S.J.; Wall, M.D.; McAllister, G.; Fischer, D.F.; Dijkstra, S.; Fratantoni, S.A.; van de Bospoort, R.; Veenman-Koepke, J.; Flynn, G.; Arjomand, J.; Dominguez, C.; Munoz-Sanjuan, I.; Wityak, J.; Bard, J.A. A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington’s disease. PLoS One, 2014, 9(2), e87923.
[] [PMID: 24503862]
Simmons, D.A.; Belichenko, N.P.; Yang, T.; Condon, C.; Monbureau, M.; Shamloo, M.; Jing, D.; Massa, S.M.; Longo, F.M. A small molecule TrkB ligand reduces motor impairment and neuropathology in R6/2 and BACHD mouse models of Huntington’s disease. J. Neurosci., 2013, 33(48), 18712-18727.
[] [PMID: 24285878]
Jiang, M.; Peng, Q.; Liu, X.; Jin, J.; Hou, Z.; Zhang, J.; Mori, S.; Ross, C.A.; Ye, K.; Duan, W. Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington’s disease. Hum. Mol. Genet., 2013, 22(12), 2462-2470.
[] [PMID: 23446639]
Conforti, P.; Zuccato, C.; Gaudenzi, G.; Ieraci, A.; Camnasio, S.; Buckley, N.J.; Mutti, C.; Cotelli, F.; Contini, A.; Cattaneo, E. Binding of the repressor complex REST-mSIN3b by small molecules restores neuronal gene transcription in Huntington’s disease models. J. Neurochem., 2013, 127(1), 22-35.
[] [PMID: 23800350]
Charbord, J.; Poydenot, P.; Bonnefond, C.; Feyeux, M.; Casagrande, F.; Brinon, B.; Francelle, L.; Aurégan, G.; Guillermier, M.; Cailleret, M.; Viegas, P.; Nicoleau, C.; Martinat, C.; Brouillet, E.; Cattaneo, E.; Peschanski, M.; Lechuga, M.; Perrier, A.L. High throughput screening for inhibitors of REST in neural derivatives of human embryonic stem cells reveals a chemical compound that promotes expression of neuronal genes. Stem Cells, 2013, 31(9), 1816-1828.
[] [PMID: 23712629]
Mielcarek, M.; Landles, C.; Weiss, A.; Bradaia, A.; Seredenina, T.; Inuabasi, L.; Osborne, G.F.; Wadel, K.; Touller, C.; Butler, R.; Robertson, J.; Franklin, S.A.; Smith, D.L.; Park, L.; Marks, P.A.; Wanker, E.E.; Olson, E.N.; Luthi-Carter, R.; van der Putten, H.; Beaumont, V.; Bates, G.P. HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration. PLoS Biol., 2013, 11(11), e1001717.
[] [PMID: 24302884]
Thomas, E.A.; Coppola, G.; Desplats, P.A.; Tang, B.; Soragni, E.; Burnett, R.; Gao, F.; Fitzgerald, K.M.; Borok, J.F.; Herman, D.; Geschwind, D.H.; Gottesfeld, J.M. The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington’s disease transgenic mice. Proc. Natl. Acad. Sci. USA, 2008, 105(40), 15564-15569.
[] [PMID: 18829438]
Jia, H.; Pallos, J.; Jacques, V.; Lau, A.; Tang, B.; Cooper, A.; Syed, A.; Purcell, J.; Chen, Y.; Sharma, S.; Sangrey, G.R.; Darnell, S.B.; Plasterer, H.; Sadri-Vakili, G.; Gottesfeld, J.M.; Thompson, L.M.; Rusche, J.R.; Marsh, J.L.; Thomas, E.A. Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington’s disease. Neurobiol. Dis., 2012, 46(2), 351-361.
[] [PMID: 22590724]
Jia, H.; Morris, C.D.; Williams, R.M.; Loring, J.F.; Thomas, E.A. HDAC inhibition imparts beneficial transgenerational effects in Huntington’s disease mice via altered DNA and histone methylation. Proc. Natl. Acad. Sci. USA, 2015, 12(1), 56-64.
[] [PMID: 25535382]
Puigserver, P.; Rhee, J.; Donovan, J.; Walkey, C.J.; Yoon, J.C.; Oriente, F.; Kitamura, Y.; Altomonte, J.; Dong, H.; Accili, D.; Spiegelman, B.M. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature, 2003, 423(6939), 550-555.
[] [PMID: 12754525]
Chiang, M.C.; Chen, C.M.; Lee, M.R.; Chen, H.W.; Chen, H.M.; Wu, Y.S.; Hung, C.H.; Kang, J.J.; Chang, C.P.; Chang, C.; Wu, Y.R.; Tsai, Y.S.; Chern, Y. Modulation of energy deficiency in Huntington’s disease via activation of the peroxisome proliferator-activated receptor gamma. Hum. Mol. Genet., 2010, 19(20), 4043-4058.
[] [PMID: 20668093]
Quintanilla, R.A.; Jin, Y.N.; Fuenzalida, K.; Bronfman, M.; Johnson, G.V. Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease. J. Biol. Chem., 2008, 283(37), 25628-25637.
[] [PMID: 18640979]
Johri, A.; Calingasan, N.Y.; Hennessey, T.M.; Sharma, A.; Yang, L.; Wille, E.; Chandra, A.; Beal, M.F. Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington’s disease. Hum. Mol. Genet., 2012, 21(5), 1124-1137.
[] [PMID: 22095692]
Yatsuga, S.; Suomalainen, A. Effect of bezafibrate treatment on late-onset mitochondrial myopathy in mice. Hum. Mol. Genet., 2012, 21(3), 526-535.
[] [PMID: 22012983]
Naia, L.; Rosenstock, T.R.; Oliveira, A.M.; Oliveira-Sousa, S.I.; Caldeira, G.L.; Carmo, C.; Laço, M.N.; Hayden, M.R.; Oliveira, C.R.; Rego, A.C. Comparative mitochondrial-based protective effects of resveratrol and nicotinamide in Huntington’s disease models. Mol. Neurobiol., 2017, 54(7), 5385-5399.
[] [PMID: 27590140]
McGarry, A.; McDermott, M.; Kieburtz, K.; de Blieck, E.A.; Beal, F.; Marder, K.; Ross, C.; Shoulson, I.; Gilbert, P.; Mallonee, W.M.; Guttman, M.; Wojcieszek, J.; Kumar, R.; LeDoux, M.S.; Jenkins, M.; Rosas, H.D.; Nance, M.; Biglan, K.; Como, P.; Dubinsky, R.M.; Shannon, K.M.; O’Suilleabhain, P.; Chou, K.; Walker, F.; Martin, W.; Wheelock, V.L.; McCusker, E.; Jankovic, J.; Singer, C.; Sanchez-Ramos, J.; Scott, B.; Suchowersky, O.; Factor, S.A.; Higgins, D.S., Jr; Molho, E.; Revilla, F.; Caviness, J.N.; Friedman, J.H.; Perlmutter, J.S.; Feigin, A.; Anderson, K.; Rodriguez, R.; McFarland, N.R.; Margolis, R.L.; Farbman, E.S.; Raymond, L.A.; Suski, V.; Kostyk, S.; Colcher, A.; Seeberger, L.; Epping, E.; Esmail, S.; Diaz, N.; Fung, W.L.; Diamond, A.; Frank, S.; Hanna, P.; Hermanowicz, N.; Dure, L.S.; Cudkowicz, M. Huntington Study Group 2CARE Investigators and Coordinators. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology, 2017, 88(2), 152-159.
[] [PMID: 27913695]
Jiang, J.; Kurnikov, I.; Belikova, N.A.; Xiao, J.; Zhao, Q.; Amoscato, A.A.; Braslau, R.; Studer, A.; Fink, M.P.; Greenberger, J.S.; Wipf, P.; Kagan, V.E. Structural requirements for optimized delivery, inhibition of oxidative stress, and antiapoptotic activity of targeted nitroxides. J. Pharmacol. Exp. Ther., 2007, 320(3), 1050-1060.
[] [PMID: 17179468]
Xun, Z.; Rivera-Sánchez, S.; Ayala-Peña, S.; Lim, J.; Budworth, H.; Skoda, E.M.; Robbins, P.D.; Niedernhofer, L.J.; Wipf, P.; McMurray, C.T. Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington’s disease. Cell Rep., 2012, 2(5), 1137-1142.
[] [PMID: 23122961]
Polyzos, A.A.; Wood, N.I.; Williams, P.; Wipf, P.; Morton, A.J.; McMurray, C.T. XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington’s disease is age- and sex- dependent. PLoS One, 2018, 13(4), e0194580.
[] [PMID: 29630611]
Reis, S.D.; Pinho, B.R.; Oliveira, J.M.A. Modulation of molecular chaperones in Huntington’s disease and other polyglutamine disorders. Mol. Neurobiol., 2017, 54(8), 5829-5854.
[] [PMID: 27660272]
Baldo, B.; Weiss, A.; Parker, C.N.; Bibel, M.; Paganetti, P.; Kaupmann, K. A screen for enhancers of clearance identifies huntingtin as a heat shock protein 90 (Hsp90) client protein. J. Biol. Chem., 2012, 287(2), 1406-1414.
[] [PMID: 22123826]
Labbadia, J.; Cunliffe, H.; Weiss, A.; Katsyuba, E.; Sathasivam, K.; Seredenina, T.; Woodman, B.; Moussaoui, S.; Frentzel, S.; Luthi-Carter, R.; Paganetti, P.; Bates, G.P. Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease. J. Clin. Invest., 2011, 121(8), 3306-3319.
[] [PMID: 21785217]
Orozco-Díaz, R.; Sánchez-Álvarez, A.; Hernández-Hernández, J.M.; Tapia-Ramírez, J. The interaction between RE1-silencing transcription factor (REST) and heat shock protein 90 as new therapeutic target against Huntington’s disease. PLoS One, 2019, 14(7), e0220393.
[] [PMID: 31361762]
Dobson, L.; Träger, U.; Farmer, R.; Hayardeny, L.; Loupe, P.; Hayden, M.R.; Tabrizi, S.J. Laquinimod dampens hyperactive cytokine production in Huntington’s disease patient myeloid cells. J. Neurochem., 2016, 137(5), 782-794.
[] [PMID: 26823290]
Gupta, S.; Sharma, B. Pharmacological benefit of I(1)-imidazoline receptors activation and nuclear factor kappa-B (NF-κB) modulation in experimental Huntington’s disease. Brain Res. Bull., 2014, 102, 57-68.
[] [PMID: 24582883]
Brouillet, E.; Jenkins, B.G.; Hyman, B.T.; Ferrante, R.J.; Kowall, N.W.; Srivastava, R.; Roy, D.S.; Rosen, B.R.; Beal, M.F. Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J. Neurochem., 1993, 60(1), 356-359.
[] [PMID: 8417157]
Bouchard, J.; Truong, J.; Bouchard, K.; Dunkelberger, D.; Desrayaud, S.; Moussaoui, S.; Tabrizi, S.J.; Stella, N.; Muchowski, P.J. Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington’s disease. J. Neurosci., 2012, 32(50), 18259-18268.
[] [PMID: 23238740]
Hsiao, H.Y.; Chen, Y.C.; Chen, H.M.; Tu, P.H.; Chern, Y. A critical role of astrocyte-mediated nuclear factor-κB-dependent inflammation in Huntington’s disease. Hum. Mol. Genet., 2013, 22(9), 1826-1842.
[] [PMID: 23372043]
Bowles, K.R.; Stone, T.; Holmans, P.; Allen, N.D.; Dunnett, S.B.; Jones, L. SMAD transcription factors are altered in cell models of HD and regulate HTT expression. Cell. Signal., 2017, 31, 1-14.
[] [PMID: 27988204]
Ament, S.A.; Pearl, J.R.; Cantle, J.P.; Bragg, R.M.; Skene, P.J.; Coffey, S.R.; Bergey, D.E.; Wheeler, V.C.; MacDonald, M.E.; Baliga, N.S.; Rosinski, J.; Hood, L.E.; Carroll, J.B.; Price, N.D. Transcriptional regulatory networks underlying gene expression changes in Huntington’s disease. Mol. Syst. Biol., 2018, 14(3), e7435.
[] [PMID: 29581148]
Seredenina, T.; Luthi-Carter, R. What have we learned from gene expression profiles in Huntington’s disease? Neurobiol. Dis., 2012, 45(1), 83-98.
[] [PMID: 21820514]
Niewiadomska-Cimicka, A.; Krzyżosiak, A.; Ye, T.; Podleśny-Drabiniok, A.; Dembélé, D.; Dollé, P.; Krężel, W. Genome-wide analysis of RARb transcriptional targets in mouse striatum links retinoic acid signaling with Huntington’s disease and other neurodegenerative disorders. Mol. Neurobiol., 2017, 54(5), 3859-3878.
[] [PMID: 27405468]
Neueder, A.; Bates, G.P. A common gene expression signature in Huntington’s disease patient brain regions. BMC Med. Genomics, 2014, 7, 60.
[] [PMID: 25358814]
Mielcarek, M.; Bondulich, M.K.; Inuabasi, L.; Franklin, S.A.; Muller, T.; Bates, G.P. The Huntington’s disease-related cardiomyopathy prevents a hypertrophic response in the R6/2 mouse model. PLoS One, 2014, 9(9), e108961.
[] [PMID: 25268775]
Ravache, M.; Weber, C.; Mérienne, K.; Trottier, Y. Transcriptional activation of REST by Sp1 in Huntington’s disease models. PLoS One, 2010, 5(12), e14311.
[] [PMID: 21179468]
Vodicka, P.; Chase, K.; Iuliano, M.; Tousley, A.; Valentine, D.T.; Sapp, E.; Kegel-Gleason, K.B.; Sena-Esteves, M.; Aronin, N.; DiFiglia, M. Autophagy activation by transcription factor EB (TFEB) in striatum of HDQ175/Q7Mice. J. Huntingtons Dis., 2016, 5(3), 249-260.
[] [PMID: 27689619]
Moily, N.S.; Ormsby, A.R.; Stojilovic, A.; Ramdzan, Y.M.; Diesch, J.; Hannan, R.D.; Zajac, M.S.; Hannan, A.J.; Oshlack, A.; Hatters, D.M. Transcriptional profiles for distinct aggregation states of mutant Huntingtin exon 1 protein unmask new Huntington’s disease pathways. Mol. Cell. Neurosci., 2017, 83, 103-112.
[] [PMID: 28743452]
Hayashida, N.; Fujimoto, M.; Tan, K.; Prakasam, R.; Shinkawa, T.; Li, L.; Ichikawa, H.; Takii, R.; Nakai, A. Heat shock factor 1 ameliorates proteotoxicity in cooperation with the transcription factor NFAT. EMBO J., 2010, 29(20), 3459-3469.
[] [PMID: 20834230]
Vidal, R.L.; Figueroa, A.; Court, F.A.; Thielen, P.; Molina, C.; Wirth, C.; Caballero, B.; Kiffin, R.; Segura-Aguilar, J.; Cuervo, A.M.; Glimcher, L.H.; Hetz, C. Targeting the UPR transcription factor XBP1 protects against Huntington’s disease through the regulation of FoxO1 and autophagy. Hum. Mol. Genet., 2012, 21(10), 2245-2262.
[] [PMID: 22337954]
Anglada-Huguet, M.; Giralt, A.; Perez-Navarro, E.; Alberch, J.; Xifró, X. Activation of Elk-1 participates as a neuroprotective compensatory mechanism in models of Huntington’s disease. J. Neurochem., 2012, 121(4), 639-648.
[] [PMID: 22372926]
Kang, I.; Chu, C.T.; Kaufman, B.A. The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms. FEBS Lett., 2018, 592(5), 793-811.
[] [PMID: 29364506]
Dinkova-Kostova, A.T.; Kostov, R.V.; Kazantsev, A.G. The role of Nrf2 signaling in counteracting neurodegenerative diseases. FEBS J., 2018, 285(19), 3576-3590.
[] [PMID: 29323772]
Quinti, L.; Dayalan Naidu, S.; Träger, U.; Chen, X.; Kegel-Gleason, K.; Llères, D.; Connolly, C.; Chopra, V.; Low, C.; Moniot, S.; Sapp, E.; Tousley, A.R.; Vodicka, P.; Van Kanegan, M.J.; Kaltenbach, L.S.; Crawford, L.A.; Fuszard, M.; Higgins, M.; Miller, J.R.C.; Farmer, R.E.; Potluri, V.; Samajdar, S.; Meisel, L.; Zhang, N.; Snyder, A.; Stein, R.; Hersch, S.M.; Ellerby, L.M.; Weerapana, E.; Schwarzschild, M.A.; Steegborn, C.; Leavitt, B.R.; Degterev, A.; Tabrizi, S.J.; Lo, D.C.; DiFiglia, M.; Thompson, L.M.; Dinkova-Kostova, A.T.; Kazantsev, A.G. KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington’s disease patients. Proc. Natl. Acad. Sci. USA, 2017, 114(23), E4676-E4685.
[] [PMID: 28533375]
Hernández, I.H.; Torres-Peraza, J.; Santos-Galindo, M.; Ramos-Morón, E.; Fernández-Fernández, M.R.; Pérez-Álvarez, M.J.; Miranda-Vizuete, A.; Lucas, J.J. The neuroprotective transcription factor ATF5 is decreased and sequestered into polyglutamine inclusions in Huntington’s disease. Acta Neuropathol., 2017, 134(6), 839-850.
[] [PMID: 28861715]
Naranjo, J.R.; Zhang, H.; Villar, D.; González, P.; Dopazo, X.M.; Morón-Oset, J.; Higueras, E.; Oliveros, J.C.; Arrabal, M.D.; Prieto, A.; Cercós, P.; González, T.; De la Cruz, A.; Casado-Vela, J.; Rábano, A.; Valenzuela, C.; Gutierrez-Rodriguez, M.; Li, J-Y.; Mellström, B. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease. J. Clin. Invest., 2016, 126(2), 627-638.
[] [PMID: 26752648]

© 2024 Bentham Science Publishers | Privacy Policy