title: Epigenetic Treatment of Neuropsychiatric Disorders: Autism and Schizophrenia.
abstract: Neuropsychiatric disorders are a heterogeneous group of conditions that often share underlying mitochondrial dysfunction and biological pathways implicated in their pathogenesis, progression, and treatment. To date, these disorders have proven notoriously resistant to molecular-targeted therapies, and clinical options are relegated to interventional types, which do not address the core symptoms of the disease. In this review, we discuss emerging epigenetic-driven approaches using novel acylcarnitine esters (carnitinoids) that act on master regulators of antioxidant and cytoprotective genes and mitophagic pathways. These carnitinoids are actively transported, mitochondria-localizing, biomimetic coenzyme A surrogates of short-chain fatty acids, which inhibit histone deacetylase and may reinvigorate synaptic plasticity and protect against neuronal damage. We outline these neuroprotective effects in the context of treatment of neuropsychiatric disorders such as autism spectrum disorder and schizophrenia.
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: Department of Psychiatry, Boston Children's Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Maneta
authors.affiliation: Department of Biological Sciences, College of Arts and Sciences, The University of Alabama, Tuscaloosa, AL, USA.|Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Pinkert
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 Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Hoffman
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
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000188:drug therapy*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D057890:Epigenomics; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D018696:Neuroprotective Agents; D002331:Carnitine
keywords: Alzheimer disease; PMX-500; PMX-550; Parkinson disease; antioxidant; autism; bipolar; butyrate; carnitinoids; epigenetic; histone deacetylase; mitochondrial dysfunction; neurodegenerative; neurodevelopmental; neuropsychiatric disorders; schizophrenia