title: Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases.
abstract: Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Irwin
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA.|SRI Biosciences, A Division of SRI International, Menlo Park, CA, USA.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Moos
authors.affiliation: Cancer Research Center, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Faller
authors.affiliation: Cancer Research Center, Boston University School of Medicine, Boston, MA, USA.|PhenoMatriX, Inc., Boston, MA, USA.
authors.forename: Kosta
authors.initials: K
authors.lastname: Steliou
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.|Department of Biological Sciences, College of Arts and Sciences, The University of Alabama, Tuscaloosa, AL, USA.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Pinkert
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002331:Carnitine / Q000031:analogs & derivatives; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D056572:Histone Deacetylase Inhibitors; D002331:Carnitine
keywords: Alzheimer; PMX-500; PMX-550; Parkinson; antioxidant; butyrate; carnitine; epigenetic; histone deacetylase; histone deacetylase inhibitors; lipoic acid; mitochondrial dysfunction; neurodegeneration; post-traumatic stress disorders; reactive oxygen species