Epigenetic Treatment of Neuropsychiatric Disorders: Autism and Schizophrenia. Issue 2 (21st February 2016)

• Record Type: Journal Article
• Authors: Moos, Walter H.; Maneta, Eleni; Pinkert, Carl A.; Irwin, Michael H.; Hoffman, Michelle E.; Faller, Douglas V.; Steliou, Kosta
• Is Part Of: Drug development research. Volume 77:Issue 2(2016)
• Page Start: 53
• Page End: 72
• Publication Date: 2016-02-21
• Subjects: Alzheimer disease -- antioxidant -- autism -- bipolar -- butyrate -- carnitinoids -- epigenetic -- histone deacetylase -- mitochondrial dysfunction -- neurodegenerative -- neurodevelopmental -- neuropsychiatric disorders -- PMX‐500 -- Parkinson disease -- schizophrenia -- PMX‐550; Drug development -- Periodicals; Drugs -- Research -- Periodicals; 615.19
• DOI: 10.1002/ddr.21295
• Languages: English
• ISSNs: 0272-4391

Abstract

ABSTRACT: Preclinical Research 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. Drug Dev Res 77 : 53–72, 2016. © 2016 Wiley Periodicals, Inc.