Skip to main content
SpringerLink
Log in

HDAC Inhibitors as Novel Therapeutic Option Against Therapeutically Challenging Neurological Disorders

  • Chapter
  • First Online:
Histone Deacetylase Inhibitors — Epidrugs for Neurological Disorders

  • 278 Accesses

Abstract

Neuronal disorders are associated with transcriptional deregulation. Histone deacetylase inhibitors (HDACi) have the potential to reinstate this deregulation and as such are emerging as promising therapeutic agents for vanquishing neurological disorders. Here we discuss the marvellous therapeutic effect of various HDACi against neurological disorders including Alzheimer’s disease, Parkinson’s disease, and epilepsy. The underlying molecular players modulated by these inhibitors in bringing therapeutic effect will also be taken into consideration.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agis-Balboa RC, Pavelka Z, Kerimoglu C, Fischer A (2013) Loss of HDAC5 impairs memory function: implications for Alzheimer’s disease. J Alzheimers Dis 33(1):35–44

    Article  CAS  PubMed  Google Scholar 

  • Andreassi C, Angelozzi C, Tiziano FD, Vitali T, De Vincenzi E, Boninsegna A, Villanova M, Bertini E, Pini A, Neri G, Brahe C (2004) Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy. Eur J Hum Genet 12(1):59–65

    Article  CAS  PubMed  Google Scholar 

  • Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, Cizman Z, Di Prospero NA, Pellizzoni L, Fischbeck KH, Sumner CJ (2007) Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 117(3):659–671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bang SR, Ambavade SD, Jagdale PG, Adkar PP, Waghmare AB, Ambavade PD (2015) Lacosamide reduces HDAC levels in the brain and improves memory: potential for treatment of Alzheimer’s disease. Pharmacol Biochem Behav 134:65–69

    Article  CAS  PubMed  Google Scholar 

  • Bao J, Sharp AH, Wagster MV, Becher M, Schilling G, Ross CA, Dawson VL, Dawson TM (1996) Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin. Proc Natl Acad Sci U S A 93(10):5037–5042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brahe C, Vitali T, Tiziano FD, Angelozzi C, Pinto AM, Borgo F, Moscato U, Bertini E, Mercuri E, Neri G (2005) Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients. Eur J Hum Genet 13(2):256–259

    Article  CAS  PubMed  Google Scholar 

  • Brichta L, Hofmann Y, Hahnen E, Siebzehnrubl FA, Raschke H, Blumcke I, Eyupoglu IY, Wirth B (2003) Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet 12(19):2481–2489

    Article  CAS  PubMed  Google Scholar 

  • Buonvicino D, Felici R, Ranieri G, Caramelli R, Lapucci A, Cavone L, Muzzi M, Di Pietro L, Bernardini C, Zwergel C, Valente S, Mai A, Chiarugi A (2018) Effects of class II-selective histone deacetylase inhibitor on neuromuscular function and disease progression in SOD1-ALS mice. Neuroscience 379:228–238

    Article  CAS  PubMed  Google Scholar 

  • Calder AN, Androphy EJ, Hodgetts KJ (2016) Small molecules in development for the treatment of spinal muscular atrophy. J Med Chem 59(22):10067–10083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang JG, Hsieh-Li HM, Jong YJ, Wang NM, Tsai CH, Li H (2001) Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A 98(17):9808–9813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang X, Rong C, Chen Y, Yang C, Hu Q, Mo Y, Zhang C, Gu X, Zhang L, He W, Cheng S, Hou X, Su R, Liu S, Dun W, Wang Q, Fang S (2015) (−)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer’s disease model mice by upregulating neprilysin expression. Exp Cell Res 334(1):136–145

    Article  CAS  PubMed  Google Scholar 

  • Chen PS, Peng GS, Li G, Yang S, Wu X, Wang CC, Wilson B, Lu RB, Gean PW, Chuang DM, Hong JS (2006) Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry 11(12):1116–1125

    Article  CAS  PubMed  Google Scholar 

  • Chen SH, Wu HM, Ossola B, Schendzielorz N, Wilson BC, Chu CH, Chen SL, Wang Q, Zhang D, Qian L, Li X, Hong JS, Lu RB (2012) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, protects dopaminergic neurons from neurotoxin-induced damage. Br J Pharmacol 165(2):494–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Citraro R, Leo A, Santoro M, D’Agostino G, Constanti A, Russo E (2017) Role of Histone Deacetylases (HDACs) in epilepsy and epileptogenesis. Curr Pharm Des 23(37):5546–5562

    Article  CAS  PubMed  Google Scholar 

  • Cook C, Carlomagno Y, Gendron TF, Dunmore J, Scheffel K, Stetler C, Davis M, Dickson D, Jarpe M, DeTure M, Petrucelli L (2014) Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Hum Mol Genet 23(1):104–116

    Article  CAS  PubMed  Google Scholar 

  • Cudkowicz ME, Andres PL, Macdonald SA, Bedlack RS, Choudry R, Brown RH Jr, Zhang H, Schoenfeld DA, Shefner J, Matson S, Matson WR, Ferrante RJ (2009) Phase 2 study of sodium phenylbutyrate in ALS. Amyotroph Lateral Scler 10(2):99–106

    Article  CAS  PubMed  Google Scholar 

  • Devinsky O, Vezzani A, O’Brien TJ, Jette N, Scheffer IE, de Curtis M, Perucca P (2018) Epilepsy. Nat Rev Dis Primers 4:18024

    Article  PubMed  Google Scholar 

  • Ding H, Dolan PJ, Johnson GV (2008) Histone deacetylase 6 interacts with the microtubule-associated protein tau. J Neurochem 106(5):2119–2130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans MC, Cherry JJ, Androphy EJ (2011) Differential regulation of the SMN2 gene by individual HDAC proteins. Biochem Biophys Res Commun 414(1):25–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan S-J, Huang F-I, Liou J-P, Yang C-R (2018) The novel histone de acetylase 6 inhibitor, MPT0G211, ameliorates tau phosphorylation and cognitive deficits in an Alzheimer’s disease model. Cell Death Dis 9(6):655–655

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ferrante RJ, Kubilus JK, Lee J, Ryu H, Beesen A, Zucker B, Smith K, Kowall NW, Ratan RR, Luthi-Carter R, Hersch SM (2003) Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington’s disease mice. J Neurosci 23(28):9418–9427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganai SA (2017) Small-molecule modulation of HDAC6 activity: the propitious therapeutic strategy to vanquish neurodegenerative disorders. Curr Med Chem 8(81646). https://doi.org/10.2174/0929867324666170209104030

  • Ganai SA, Kalladi SM, Mahadevan V (2015) HDAC inhibition through valproic acid modulates the methylation profiles in human embryonic kidney cells. J Biomol Struct Dyn 33(6):1185–1197

    Article  CAS  PubMed  Google Scholar 

  • Ganai SA, Ramadoss M, Mahadevan V (2016) Histone deacetylase (HDAC) inhibitors – emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration. Curr Neuropharmacol 14(1):55–71

    Article  CAS  PubMed  Google Scholar 

  • Garbes L, Riessland M, Holker I, Heller R, Hauke J, Trankle C, Coras R, Blumcke I, Hahnen E, Wirth B (2009) LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate. Hum Mol Genet 18(19):3645–3658

    Article  CAS  PubMed  Google Scholar 

  • Gardian G, Yang L, Cleren C, Calingasan NY, Klivenyi P, Beal MF (2004) Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity. NeuroMolecular Med 5(3):235–241

    Article  CAS  PubMed  Google Scholar 

  • Gerstner T, Bell N, König S (2008) Oral valproic acid for epilepsy – long-term experience in therapy and side effects. Expert Opin Pharmacother 9(2):285–292

    Article  CAS  PubMed  Google Scholar 

  • Göttlicher M, Minucci S, Zhu P, Krämer OH, Schimpf A, Giavara S, Sleeman JP, Lo Coco F, Nervi C, Pelicci PG, Heinzel T (2001) Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 20(24):6969–6978

    Article  PubMed  PubMed Central  Google Scholar 

  • Guan J-S, Haggarty SJ, Giacometti E, Dannenberg J-H, Joseph N, Gao J, Nieland TJF, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai L-H (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459(7243):55–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo W, Naujock M, Fumagalli L, Vandoorne T, Baatsen P, Boon R, Ordovás L, Patel A, Welters M, Vanwelden T, Geens N, Tricot T, Benoy V, Steyaert J, Lefebvre-Omar C, Boesmans W, Jarpe M, Sterneckert J, Wegner F, Petri S, Bohl D, Vanden Berghe P, Robberecht W, Van Damme P, Verfaillie C, Van Den Bosch L (2017) HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nat Commun 8(1):861

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hahnen E, Eyupoglu IY, Brichta L, Haastert K, Trankle C, Siebzehnrubl FA, Riessland M, Holker I, Claus P, Romstock J, Buslei R, Wirth B, Blumcke I (2006) In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy. J Neurochem 98(1):193–202

    Article  CAS  PubMed  Google Scholar 

  • Hardy J (2006) A hundred years of Alzheimer’s disease research. Neuron 52(1):3–13

    Article  CAS  PubMed  Google Scholar 

  • Harrison IF, Smith AD, Dexter DT (2018) Pathological histone acetylation in Parkinson’s disease: neuroprotection and inhibition of microglial activation through SIRT 2 inhibition. Neurosci Lett 666:48–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hauke J, Riessland M, Lunke S, Eyupoglu IY, Blumcke I, El-Osta A, Wirth B, Hahnen E (2009) Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition. Hum Mol Genet 18(2):304–317

    Article  CAS  PubMed  Google Scholar 

  • Hegarty S, Sullivan A, O’Keeffe G (2016) The epigenome as a therapeutic target for Parkinson’s disease. Neural Regen Res 11(11):1735–1738

    Article  PubMed  PubMed Central  Google Scholar 

  • Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8(4):382–397

    Article  CAS  PubMed  Google Scholar 

  • Hockly E, Richon VM, Woodman B, Smith DL, Zhou X, Rosa E, Sathasivam K, Ghazi-Noori S, Mahal A, Lowden PA, Steffan JS, Marsh JL, Thompson LM, Lewis CM, Marks PA, Bates GP (2003) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 100(4):2041–2046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu Q-P, Mao D-A (2016) Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation. BMC Neurosci 17(1):22. https://doi.org/10.1186/s12868-016-0264-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janssen C, Schmalbach S, Boeselt S, Sarlette A, Dengler R, Petri S (2010) Differential histone deacetylase mRNA expression patterns in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 69(6):573–581

    Article  CAS  PubMed  Google Scholar 

  • Jeong H, Then F, Melia TJ Jr, Mazzulli JR, Cui L, Savas JN, Voisine C, Paganetti P, Tanese N, Hart AC, Yamamoto A, Krainc D (2009) Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell 137(1):60–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia H, Morris CD, Williams RM, Loring JF, Thomas EA (2015) HDAC inhibition imparts beneficial transgenerational effects in Huntington’s disease mice via altered DNA and histone methylation. Proc Natl Acad Sci U S A 112(1):22

    Article  CAS  Google Scholar 

  • Johnston TH, Huot P, Damude S, Fox SH, Jones SW, Rusche JR, Brotchie JM (2013) RGFP109, a histone deacetylase inhibitor attenuates L-DOPA-induced dyskinesia in the MPTP-lesioned marmoset: a proof-of-concept study. Parkinsonism Relat Disord 19(2):260–264

    Article  PubMed  Google Scholar 

  • Kellinghaus C (2009) Lacosamide as treatment for partial epilepsy: mechanisms of action, pharmacology, effects, and safety. Ther Clin Risk Manag 5:757–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kidd SK, Schneider JS (2010) Protection of dopaminergic cells from MPP+-mediated toxicity by histone deacetylase inhibition. Brain Res 1:172–178

    Article  CAS  Google Scholar 

  • Kidd SK, Schneider JS (2011) Protective effects of valproic acid on the nigrostriatal dopamine system in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neuroscience 194:189–194

    Article  CAS  PubMed  Google Scholar 

  • Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, Sweatt JD, Rumbaugh G (2010) Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology 35(4):870–880

    Article  CAS  PubMed  Google Scholar 

  • Kusaczuk M, Krętowski R, Bartoszewicz M, Cechowska-Pasko M (2015) Phenylbutyrate-a pan-HDAC inhibitor-suppresses proliferation of glioblastoma LN-229 cell line. Tumour Biol 37(1):931–942. https://doi.org/10.1007/s13277-015-3781-8

    Article  CAS  PubMed  Google Scholar 

  • Lazo-Gómez R, Ramírez-Jarquín UN, Tovar-y-Romo LB, Tapia R (2013) Histone deacetylases and their role in motor neuron degeneration. Front Cell Neurosci 7:243

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lei P, Ayton S, Bush AI, Adlard PA (2011) GSK-3 in neurodegenerative diseases. Int J Alzheimers Dis 2011:189246

    PubMed  PubMed Central  Google Scholar 

  • Leroy K, Yilmaz Z, Brion JP (2007) Increased level of active GSK-3beta in Alzheimer’s disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration. Neuropathol Appl Neurobiol 33(1):43–55

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Yazdani A, Murray LM, Beauvais A, Kothary R (2014) The Smn-independent beneficial effects of trichostatin A on an intermediate mouse model of spinal muscular atrophy. PLoS One 9(7):e101225

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Martin HL, Teismann P (2009) Glutathione–a review on its role and significance in Parkinson’s disease. FASEB J 23(10):3263–3272

    Article  CAS  PubMed  Google Scholar 

  • Monti B, Mercatelli D, Contestabile A (2012) Valproic acid neuroprotection in 6-OHDA lesioned rat, a model for parkinson’s disease. HOAJ Biol 1(1):4. https://doi.org/10.7243/2050-0874-1-4

    Article  Google Scholar 

  • Narver HL, Kong L, Burnett BG, Choe DW, Bosch-Marce M, Taye AA, Eckhaus MA, Sumner CJ (2008) Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition. Ann Neurol 64(4):465–470

    Article  PubMed  Google Scholar 

  • Piepers S, Veldink JH, de Jong SW, van der Tweel I, van der Pol WL, Uijtendaal EV, Schelhaas HJ, Scheffer H, de Visser M, de Jong JM, Wokke JH, Groeneveld GJ, van den Berg LH (2009) Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis. Ann Neurol 66(2):227–234

    Article  CAS  PubMed  Google Scholar 

  • Price PA, Parkes JD, Marsden CD (1978) Sodium valproate in the treatment of levodopa-induced dyskinesia. J Neurol Neurosurg Psychiatry 41(8):702–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qing H, He G, Ly PT, Fox CJ, Staufenbiel M, Cai F, Zhang Z, Wei S, Sun X, Chen CH, Zhou W, Wang K, Song W (2008) Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer’s disease mouse models. J Exp Med 205(12):2781–2789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rane P, Shields J, Heffernan M, Guo Y, Akbarian S, King JA (2012) The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD. Neuropharmacology 62(7):2409–2412

    Article  CAS  PubMed  Google Scholar 

  • Reddy SD, Clossen BL, Reddy DS (2018) Epigenetic histone deacetylation inhibition prevents the development and persistence of temporal lobe epilepsy. J Pharmacol Exp Ther 364(1):97–109

    Article  CAS  PubMed  Google Scholar 

  • Ricobaraza A, Cuadrado-Tejedor M, Marco S, Perez-Otano I, Garcia-Osta A (2012) Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus 22(5):1040–1050

    Article  CAS  PubMed  Google Scholar 

  • Riessland M, Ackermann B, Forster A, Jakubik M, Hauke J, Garbes L, Fritzsche I, Mende Y, Blumcke I, Hahnen E, Wirth B (2010) SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy. Hum Mol Genet 19(8):1492–1506

    Article  CAS  PubMed  Google Scholar 

  • Rouaux C, Panteleeva I, Rene F, Gonzalez de Aguilar JL, Echaniz-Laguna A, Dupuis L, Menger Y, Boutillier AL, Loeffler JP (2007) Sodium valproate exerts neuroprotective effects in vivo through CREB-binding protein-dependent mechanisms but does not improve survival in an amyotrophic lateral sclerosis mouse model. J Neurosci 27(21):5535–5545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roy A, Ghosh A, Jana A, Liu X, Brahmachari S, Gendelman HE, Pahan K (2012) Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson’s disease. PLoS One 7(6):18

    Google Scholar 

  • Rumbaugh G, Sillivan SE, Ozkan ED, Rojas CS, Hubbs CR, Aceti M, Kilgore M, Kudugunti S, Puthanveettil SV, Sweatt JD, Rusche J, Miller CA (2015) Pharmacological selectivity within class I histone deacetylases predicts effects on synaptic function and memory rescue. Neuropsychopharmacology 40:2307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryu H, Smith K, Camelo SI, Carreras I, Lee J, Iglesias AH, Dangond F, Cormier KA, Cudkowicz ME, Brown RH Jr, Ferrante RJ (2005) Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. J Neurochem 93(5):1087–1098

    Article  CAS  PubMed  Google Scholar 

  • Sau D, De Biasi S, Vitellaro-Zuccarello L, Riso P, Guarnieri S, Porrini M, Simeoni S, Crippa V, Onesto E, Palazzolo I, Rusmini P, Bolzoni E, Bendotti C, Poletti A (2007) Mutation of SOD1 in ALS: a gain of a loss of function. Hum Mol Genet 16(13):1604–1618

    Article  CAS  PubMed  Google Scholar 

  • Sharma S, Taliyan R (2015) Targeting histone deacetylases: a novel approach in Parkinson’s disease. Park Dis 2015:11

    Google Scholar 

  • Siebzehnrubl FA, Raber KA, Urbach YK, Schulze-Krebs A, Canneva F, Moceri S, Habermeyer J, Achoui D, Gupta B, Steindler DA, Stephan M, Nguyen HP, Bonin M, Riess O, Bauer A, Aigner L, Couillard-Despres S, Paucar MA, Svenningsson P, Osmand A, Andreew A, Zabel C, Weiss A, Kuhn R, Moussaoui S, Blockx I, Van der Linden A, Cheong RY, Roybon L, Petersen A, von Horsten S (2018) Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition. Proc Natl Acad Sci U S A 115(37):E8765–E8774

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, Kazantsev A, Schmidt E, Zhu YZ, Greenwald M, Kurokawa R, Housman DE, Jackson GR, Marsh JL, Thompson LM (2001) Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413(6857):739–743

    Article  CAS  PubMed  Google Scholar 

  • Su Y, Ryder J, Li B, Wu X, Fox N, Solenberg P, Brune K, Paul S, Zhou Y, Liu F, Ni B (2004) Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta precursor protein processing. Biochemistry 43(22):6899–6908

    Article  CAS  PubMed  Google Scholar 

  • Suelves N, Kirkham-McCarthy L, Lahue RS, Ginés S (2017) A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington’s disease mice. Sci Rep 7(1):6082. https://doi.org/10.1038/s41598-017-05125-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugars KL, Rubinsztein DC (2003) Transcriptional abnormalities in Huntington disease. Trends Genet 19(5):233–238

    Article  CAS  PubMed  Google Scholar 

  • Suo H, Wang P, Tong J, Cai L, Liu J, Huang D, Huang L, Wang Z, Huang Y, Xu J, Ma Y, Yu M, Fei J, Huang F (2015) NRSF is an essential mediator for the neuroprotection of trichostatin A in the MPTP mouse model of Parkinson’s disease. Neuropharmacology 99:67–78

    Article  CAS  PubMed  Google Scholar 

  • Valle C, Salvatori I, Gerbino V, Rossi S, Palamiuc L, René F, Carrì MT (2014) Tissue-specific deregulation of selected HDACs characterizes ALS progression in mouse models: pharmacological characterization of SIRT1 and SIRT2 pathways. Cell Death Dis 5:e1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walker FO (2007) Huntington’s disease. Lancet 369(9557):218–228

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Yang R, Gu J, Yin X, Jin N, Xie S, Chang H, Qian W, Shi J, Iqbal K, Gong CX, Cheng C, Liu F (2015) Cross talk between PI3K-AKT-GSK-3beta and PP2A pathways determines tau hyperphosphorylation. Neurobiol Aging 36(1):188–200

    Article  PubMed  CAS  Google Scholar 

  • Weihl CC, Connolly AM, Pestronk A (2006) Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy. Neurology 67(3):500–501

    Article  CAS  PubMed  Google Scholar 

  • Wu JY, Niu FN, Huang R, Xu Y (2008) Enhancement of glutamate uptake in 1-methyl-4-phenylpyridinium-treated astrocytes by trichostatin A. Neuroreport 19(12):1209–1212

    Article  CAS  PubMed  Google Scholar 

  • Yokoi N, Fukata Y, Kase D, Miyazaki T, Jaegle M, Ohkawa T, Takahashi N, Iwanari H, Mochizuki Y, Hamakubo T, Imoto K, Meijer D, Watanabe M, Fukata M (2014) Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy. Nat Med 21:19

    Article  PubMed  CAS  Google Scholar 

  • Zaitone SA, Abo-Elmatty DM, Elshazly SM (2012) Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats. Indian J Pharmacol 44(6):774–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Liu C, Wu J, Tao JJ, Sui XL, Yao ZG, Xu YF, Huang L, Zhu H, Sheng SL, Qin C (2014) Tubastatin A/ACY-1215 improves cognition in Alzheimer’s disease transgenic mice. J Alzheimers Dis 41(4):1193–1205

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Wang S, Yu L, Jin J, Ye X, Liu Y, Xu Y (2017) HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer’s disease. Aging Cell 16(5):1073–1082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Basic Sciences and Humanities, Faculty of Agriculture, SKUAST-Kashmir, Wadura Sopore, Jammu and Kashmir, India

    Shabir Ahmad Ganai

Authors
  1. Shabir Ahmad Ganai
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ganai, S.A. (2019). HDAC Inhibitors as Novel Therapeutic Option Against Therapeutically Challenging Neurological Disorders. In: Histone Deacetylase Inhibitors — Epidrugs for Neurological Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-13-8019-8_6

Download citation

Publish with us

Policies and ethics

Search

Navigation