Progress toward the development of treatment of spinal and bulbar muscular atrophy

References

• Alzheimer’s A. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016 Apr;12(4):459–509.
   Google Scholar
• Savica R, Grossardt BR, Bower JH, et al. Time trends in the incidence of parkinson disease. JAMA Neurol. 2016 Aug 01;73(8):981–989.
   Google Scholar
• Arthur KC, Calvo A, Price TR, et al. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun. 2016 Aug 11;7:12408.
   Google Scholar
• Brettschneider J, Del Tredici K, Lee VM, et al. Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci. 2015 Feb;16(2):109–120.
   Google Scholar
• Katsuno M, Tanaka F, Adachi H, et al. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA). Prog Neurobiol. 2012 Dec;99(3):246–256.
   Google Scholar
• Goodwin M, Swanson MS. RNA-binding protein misregulation in microsatellite expansion disorders. Adv Exp Med Biol. 2014;825:353–388.
   Google Scholar
• La Spada AR, Wilson EM, Lubahn DB, et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991 Jul 04;352(6330):77–79.
   Google Scholar
• Katsuno M, Adachi H, Kume A, et al. Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron. 2002 Aug 29;35(5):843–854.
   Google Scholar
• Sobue G, Doyu M, Kachi T, et al. Subclinical phenotypic expressions in heterozygous females of X-linked recessive bulbospinal neuronopathy. J Neurol Sci. 1993 Jul;117(1–2):74–78.
   Google Scholar
• Sobue G, Hashizume Y, Mukai E, et al. X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain. 1989 Feb;112(Pt 1):209–232.
   Google Scholar
• Adachi H, Katsuno M, Minamiyama M, et al. Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. Brain. 2005 Mar;128(Pt 3):659–670.
   Google Scholar
• Atsuta N, Watanabe H, Ito M, et al. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain. 2006 Jun;129(Pt 6):1446–1455.
   Google Scholar
• Suzuki K, Katsuno M, Banno H, et al. CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA. Brain. 2008 Jan;131(Pt 1):229–239.
   Google Scholar
• Rocchi C, Greco V, Urbani A, et al. Subclinical autonomic dysfunction in spinobulbar muscular atrophy (Kennedy disease). Muscle Nerve. 2011 Nov;44(5):737–740.
   Google Scholar
• Grunseich C, Kats IR, Bott LC, et al. Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat. Neuromuscul Disord. 2014 Nov;24(11):978–981.
   Google Scholar
• Lin HY, Yu IC, Wang RS, et al. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology. 2008 Jun;47(6):1924–1935.
   Google Scholar
• Araki A, Katsuno M, Suzuki K, et al. Brugada syndrome in spinal and bulbar muscular atrophy. Neurology. 2014 May 20;82(20):1813–1821.
   Google Scholar
• Querin G, Bertolin C, Da Re E, et al. Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):810–816.
   Google Scholar
• Nedelsky NB, Pennuto M, Smith RB, et al. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy. Neuron. 2010 Sep 23;67(6):936–952.
   Google Scholar
• Mano T, Katsuno M, Banno H, et al. Head lift exercise improves swallowing dysfunction in spinal and bulbar muscular atrophy. Eur Neurol. 2015;74(5–6):251–258.
   Google Scholar
• Hashizume A, Katsuno M, Banno H, et al. Longitudinal changes of outcome measures in spinal and bulbar muscular atrophy. Brain. 2012 Sep;135(Pt 9):2838–2848.
   Google Scholar
• Hijikata Y, Katsuno M, Suzuki K, et al. Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy. Ann Clin Transl Neurol. 2016 Jul;3(7):537–546.
   Google Scholar
• Nakatsuji H, Araki A, Hashizume A, et al. Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy. J Neurol. 2017 Feb 22;264:839–847.
   Google Scholar
• Orr CR, Montie HL, Liu Y, et al. An interdomain interaction of the androgen receptor is required for its aggregation and toxicity in spinal and bulbar muscular atrophy. J Biol Chem. 2010 Nov 12;285(46):35567–35577.
   Google Scholar
• Zboray L, Pluciennik A, Curtis D, et al. Preventing the androgen receptor N/C interaction delays disease onset in a mouse model of SBMA. Cell Rep. 2015 Dec 15;13(10):2312–2323.
   Google Scholar
• Tanaka F, Reeves MF, Ito Y, et al. Tissue-specific somatic mosaicism in spinal and bulbar muscular atrophy is dependent on CAG-repeat length and androgen receptor–gene expression level. Am J Hum Genet. 1999 Oct;65(4):966–973.
   Google Scholar
• Doyu M, Sobue G, Mukai E, et al. Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene. Ann Neurol. 1992 Nov;32(5):707–710.
   Google Scholar
• Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res. 1994 Aug 11;22(15):3181–3186.
   Google Scholar
• Jones L, Houlden H, Tabrizi SJ. DNA repair in the trinucleotide repeat disorders. Lancet Neurol. 2017 Jan;16(1):88–96.
   Google Scholar
• Li M, Miwa S, Kobayashi Y, et al. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol. 1998 Aug;44(2):249–254.
   Google Scholar
• Palazzolo I, Stack C, Kong L, et al. Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron. 2009 Aug 13;63(3):316–328.
   Google Scholar
• Scaramuzzino C, Casci I, Parodi S, et al. Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy. Neuron. 2015 Jan 07;85(1):88–100.
   Google Scholar
• Katsuno M, Adachi H, Minamiyama M, et al. Disrupted transforming growth factor-β signaling in spinal and bulbar muscular atrophy. J Neurosci. 2010 Apr 21;30(16):5702–5712.
   Google Scholar
• Cortes CJ, Ling SC, Guo LT, et al. Muscle expression of mutant androgen receptor accounts for systemic and motor neuron disease phenotypes in spinal and bulbar muscular atrophy. Neuron. 2014 Apr 16;82(2):295–307.
   Google Scholar
• Lieberman AP, Yu Z, Murray S, et al. Peripheral androgen receptor gene suppression rescues disease in mouse models of spinal and bulbar muscular atrophy. Cell Rep. 2014 May 08;7(3):774–784.
   Google Scholar
• Katsuno M, Adachi H, Minamiyama M, et al. Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration. J Neurosci. 2006 Nov 22;26(47):12106–12117.
   Google Scholar
• Monks DA, Johansen JA, Mo K, et al. Overexpression of wild-type androgen receptor in muscle recapitulates polyglutamine disease. Proc Natl Acad Sci USA. 2007 Nov 13;104(46):18259–18264.
   Google Scholar
• Sopher BL, Thomas PS Jr., LaFevre-Bernt MA, et al. Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration. Neuron. 2004 Mar 04;41(5):687–699.
   Google Scholar
• Yu Z, Dadgar N, Albertelli M, et al. Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy disease phenotype in a mouse knock-in model. J Clin Invest. 2006 Oct;116(10):2663–2672.
   Google Scholar
• Halievski K, Henley CL, Domino L, et al. Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA. Exp Neurol. 2015;269:224–232.
   Google Scholar
• Ding Y, Adachi H, Katsuno M, et al. Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration. Biochem Biophys Res Commun. 2015 Dec 25;468(4):677–683.
   Google Scholar
• Rinaldi C, Bott LC, Chen KL, et al. Insulinlike growth factor (IGF)-1 administration ameliorates disease manifestations in a mouse model of spinal and bulbar muscular atrophy. Mol Med. 2012 Dec 06;18:1261–1268.
   Google Scholar
• Palazzolo I, Burnett BG, Young JE, et al. Akt blocks ligand binding and protects against expanded polyglutamine androgen receptor toxicity. Hum Mol Genet. 2007 Jul 01;16(13):1593–1603.
   Google Scholar
• LaFevre-Bernt MA, Ellerby LM. Kennedy’s disease. Phosphorylation of the polyglutamine-expanded form of androgen receptor regulates its cleavage by caspase-3 and enhances cell death. J Biol Chem. 2003 Sep 12;278(37):34918–34924.
   Google Scholar
• Polanco MJ, Parodi S, Piol D, et al. Adenylyl cyclase activating polypeptide reduces phosphorylation and toxicity of the polyglutamine-expanded androgen receptor in spinobulbar muscular atrophy. Sci Transl Med. 2016 Dec 21;8(370):370ra181.
   Google Scholar
• Todd TW, Kokubu H, Miranda HC, et al. Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophy. Elife. 2015 Aug;26(4):e08493.
   Google Scholar
• Montie HL, Pestell RG, Merry DE. SIRT1 modulates aggregation and toxicity through deacetylation of the androgen receptor in cell models of SBMA. J Neurosci. 2011 Nov 30;31(48):17425–17436.
   Google Scholar
• Dai Y, Ngo D, Forman LW, et al. Sirtuin 1 is required for antagonist-induced transcriptional repression of androgen-responsive genes by the androgen receptor. Mol Endocrinol. 2007 Aug;21(8):1807–1821.
   Google Scholar
• Fu M, Wang C, Reutens AT, et al. p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. J Biol Chem. 2000 Jul 07;275(27):20853–20860.
   Google Scholar
• Poukka H, Karvonen U, Janne OA, et al. Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc Natl Acad Sci USA. 2000 Dec 19;97(26):14145–14150.
   Google Scholar
• Chua JP, Reddy SL, Yu Z, et al. Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor-mediated disease. J Clin Invest. 2015 Feb;125(2):831–845.
   Google Scholar
• Zu T, Gibbens B, Doty NS, et al. Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci USA. 2011 Jan 04;108(1):260–265.
   Google Scholar
• Kramer NJ, Carlomagno Y, Zhang YJ, et al. Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts. Science. 2016 Aug 12;353(6300):708–712.
   Google Scholar
• Cheng HM, Chern Y, Chen IH, et al. Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown. Plos Genet. 2015 Mar;11(3):e1005043.
   Google Scholar
• Miyazaki Y, Adachi H, Katsuno M, et al. Viral delivery of miR-196a ameliorates the SBMA phenotype via the silencing of CELF2. Nat Med. 2012 Jul;18(7):1136–1141.
   Google Scholar
• Pourshafie N, Lee PR, Chen KL, et al. MiR-298 counteracts mutant androgen receptor toxicity in spinal and bulbar muscular atrophy. Mol Ther. 2016 May;24(5):937–945.
   Google Scholar
• Pecho-Vrieseling E, Rieker C, Fuchs S, et al. Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons. Nat Neurosci. 2014 Aug;17(8):1064–1072.
   Google Scholar
• Jeon I, Cicchetti F, Cisbani G, et al. Human-to-mouse prion-like propagation of mutant huntingtin protein. Acta Neuropathol. 2016 Oct;132(4):577–592.
   Google Scholar
• Iguchi Y, Eid L, Parent M, et al. Exosome secretion is a key pathway for clearance of pathological TDP-43. Brain. 2016 Dec;139(Pt 12):3187–3201.
   Google Scholar
• Minamiyama M, Katsuno M, Adachi H, et al. Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract. Nat Med. 2012 Oct;18(10):1531–1538.
   Google Scholar
• Xu Y, Halievski K, Henley C, et al. Defects in neuromuscular transmission may underlie motor dysfunction in spinal and bulbar muscular atrophy. J Neurosci. 2016 May 04;36(18):5094–5106.
   Google Scholar
• Ranganathan S, Harmison GG, Meyertholen K, et al. Mitochondrial abnormalities in spinal and bulbar muscular atrophy. Hum Mol Genet. 2009 Jan 01;18(1):27–42.
   Google Scholar
• Rocchi A, Milioto C, Parodi S, et al. Glycolytic-to-oxidative fiber-type switch and mTOR signaling activation are early-onset features of SBMA muscle modified by high-fat diet. Acta Neuropathol. 2016 Jul;132(1):127–144.
   Google Scholar
• Giorgetti E, Yu Z, Chua JP, et al. Rescue of metabolic alterations in AR113Q skeletal muscle by peripheral androgen receptor gene silencing. Cell Rep. 2016 Sep 27;17(1):125–136.
   Google Scholar
• Yamada S, Hashizume A, Hijikata Y, et al. Decreased peak expiratory flow associated with muscle fiber-type switching in spinal and bulbar muscular atrophy. Plos One. 2016;11(12):e0168846.66.
   Google Scholar
• Finley D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem. 2009;78:477–513.
   Google Scholar
• Pratt WB, Gestwicki JE, Osawa Y, et al. Targeting Hsp90/Hsp70-based protein quality control for treatment of adult onset neurodegenerative diseases. Annu Rev Pharmacol Toxicol. 2015;55:353–371.
   Google Scholar
• Kondo N, Katsuno M, Adachi H, et al. Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration. Nat Commun. 2013;4:1405.
   Google Scholar
• Doi H, Adachi H, Katsuno M, et al. p62/SQSTM1 differentially removes the toxic mutant androgen receptor via autophagy and inclusion formation in a spinal and bulbar muscular atrophy mouse model. J Neurosci. 2013 May 01;33(18):7710–7727.
   Google Scholar
• Pandey UB, Nie Z, Batlevi Y, et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature. 2007 Jun 14;447(7146):859–863.
   Google Scholar
• Cortes CJ, Miranda HC, Frankowski H, et al. Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA. Nat Neurosci. 2014 Sep;17(9):1180–1189.
   Google Scholar
• Young JE, Garden GA, Martinez RA, et al. Polyglutamine-expanded androgen receptor truncation fragments activate a Bax-dependent apoptotic cascade mediated by DP5/Hrk. J Neurosci. 2009 Feb 18;29(7):1987–1997.
   Google Scholar
• Beauchemin AM, Gottlieb B, Beitel LK, et al. Cytochrome c oxidase subunit Vb interacts with human androgen receptor: a potential mechanism for neurotoxicity in spinobulbar muscular atrophy. Brain Res Bull. 2001 Oct-Nov 1;56(3–4):285–297.
   Google Scholar
• Iida M, Katsuno M, Nakatsuji H, et al. Pioglitazone suppresses neuronal and muscular degeneration caused by polyglutamine-expanded androgen receptors. Hum Mol Genet. 2015 Jan 15;24(2):314–329.
   Google Scholar
• Katsuno M, Adachi H, Doyu M, et al. Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat Med. 2003 Jun;9(6):768–773.
   Google Scholar
• Renier KJ, Troxell-Smith SM, Johansen JA, et al. Antiandrogen flutamide protects male mice from androgen-dependent toxicity in three models of spinal bulbar muscular atrophy. Endocrinology. 2014 Jul;155(7):2624–2634.
   Google Scholar
• Katsuno M, Banno H, Suzuki K, et al. Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular atrophy (JASMITT study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 Sep;9(9):875–884.
   Google Scholar
• Banno H, Katsuno M, Suzuki K, et al. Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy. Ann Neurol. 2009 Feb;65(2):140–150.
   Google Scholar
• Banno H, Adachi H, Katsuno M, et al. Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: a pathogenic marker. Ann Neurol. 2006 Mar;59(3):520–526.
   Google Scholar
• Fernandez-Rhodes LE, Kokkinis AD, White MJ, et al. Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):140–147.
   Google Scholar
• Li M, Sobue G, Doyu M, et al. Primary sensory neurons in X-linked recessive bulbospinal neuropathy: histopathology and androgen receptor gene expression. Muscle Nerve. 1995 Mar;18(3):301–308.
   Google Scholar
• Ramzan F, McPhail M, Rao P, et al. Distinct etiological roles for myocytes and motor neurons in a mouse model of kennedy’s disease/spinobulbar muscular atrophy. J Neurosci. 2015 Apr 22;35(16):6444–6451.
   Google Scholar
• Sahashi K, Katsuno M, Hung G, et al. Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet. 2015 Nov 01;24(21):5985–5994.
   Google Scholar
• Stenoien DL, Cummings CJ, Adams HP, et al. Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum Mol Genet. 1999 May;8(5):731–741.
   Google Scholar
• Tokui K, Adachi H, Waza M, et al. 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse. Hum Mol Genet. 2009 Mar 01;18(5):898–910.
   Google Scholar
• Li M, Chevalier-Larsen ES, Merry DE, et al. Soluble androgen receptor oligomers underlie pathology in a mouse model of spinobulbar muscular atrophy. J Biol Chem. 2007 Feb 02;282(5):3157–3164.
   Google Scholar
• Waza M, Adachi H, Katsuno M, et al. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nat Med. 2005 Oct;11(10):1088–1095.
   Google Scholar
• Liu Y, Hettinger CL, Zhang D, et al. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington’s disease. J Neurochem. 2014 May;129(3):539–547.
   Google Scholar
• Bott LC, Badders NM, Chen KL, et al. A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy. Hum Mol Genet. 2016 May 15;25(10):1979–1989.
   Google Scholar
• Katsuno M, Sang C, Adachi H, et al. Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. Proc Natl Acad Sci USA. 2005 Nov 15;102(46):16801–16806.
   Google Scholar
• Malik B, Nirmalananthan N, Gray AL, et al. Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: implications for therapy. Brain. 2013 Mar;136(Pt 3):926–943.
   Google Scholar
• Wang AM, Miyata Y, Klinedinst S, et al. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol. 2013 Feb;9(2):112–118.
   Google Scholar
• Lee BH, Lee MJ, Park S, et al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature. 2010 Sep 09;467(7312):179–184.
   Google Scholar
• Cortes CJ, La Spada AR. Autophagy in polyglutamine disease: imposing order on disorder or contributing to the chaos? Mol Cell Neurosci. 2015 May;66(Pt A):53–61.
   Google Scholar
• Rusmini P, Crippa V, Giorgetti E, et al. Clearance of the mutant androgen receptor in motoneuronal models of spinal and bulbar muscular atrophy. Neurobiol Aging. 2013 Nov;34(11):2585–2603.
   Google Scholar
• Rusmini P, Simonini F, Crippa V, et al. 17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy. Neurobiol Dis. 2011 Jan;41(1):83–95.
   Google Scholar
• Tohnai G, Adachi H, Katsuno M, et al. Paeoniflorin eliminates a mutant AR via NF-YA-dependent proteolysis in spinal and bulbar muscular atrophy. Hum Mol Genet. 2014 Jul 01;23(13):3552–3565.
   Google Scholar
• Yu Z, Wang AM, Adachi H, et al. Macroautophagy is regulated by the UPR-mediator CHOP and accentuates the phenotype of SBMA mice. Plos Genet. 2011 Oct;7(10):e1002321.
   Google Scholar
• Milioto C, Malena A, Maino E, et al. β-agonist stimulation ameliorates the phenotype of spinal and bulbar muscular atrophy mice and patient-derived myotubes. Sci Rep. 2017 Jan 24;7:41046.
   Google Scholar
• McCampbell A, Taylor JP, Taye AA, et al. CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet. 2000 Sep 01;9(14):2197–2202.
   Google Scholar
• McCampbell A, Taye AA, Whitty L, et al. Histone deacetylase inhibitors reduce polyglutamine toxicity. Proc Natl Acad Sci USA. 2001 Dec 18;98(26):15179–15184.
   Google Scholar
• Minamiyama M, Katsuno M, Adachi H, et al. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet. 2004 Jun 01;13(11):1183–1192.
   Google Scholar
• Yang Z, Chang YJ, Yu IC, et al. ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nat Med. 2007 Mar;13(3):348–353.
   Google Scholar
• Qiang Q, Adachi H, Huang Z, et al. Genistein, a natural product derived from soybeans, ameliorates polyglutamine-mediated motor neuron disease. J Neurochem. 2013 Jul;126(1):122–130.
   Google Scholar
• Chiang MC, Chern Y, Huang RN. PPARγ rescue of the mitochondrial dysfunction in Huntington’s disease. Neurobiol Dis. 2012 Jan;45(1):322–328.
   Google Scholar
• Shrader JA, Kats I, Kokkinis A, et al. A randomized controlled trial of exercise in spinal and bulbar muscular atrophy. Ann Clin Transl Neurol. 2015 Jul;2(7):739–747.
   Google Scholar
• Rosas HD, Doros G, Gevorkian S, et al. PRECREST: a phase II prevention and biomarker trial of creatine in at-risk Huntington disease. Neurology. 2014 Mar 11;82(10):850–857.
   Google Scholar