International Journal Of Bilogical Sciences
.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 9 > Lisa Scheuing, Chi-Tso Chiu, Hsiao-Mei Liao, Gabriel R. Linares, and De-Maw Chuang
Preclinical and Clinical Investigations of Mood Stabilizers for Huntington’s Disease: What Have We Learned?
Lisa Scheuing, Chi-Tso Chiu, Hsiao-Mei Liao, Gabriel R. Linares, and De-Maw Chuang
Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive MSC 1363, Bethesda, MD 20892-1363, USA. Corresponding author: De-Maw Chuang, Ph.D. Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Building 10, Room 3D38, 10 Center Drive, MSC 1363, Bethesda, MD 20892-1363, USA. Tel: 301-496-4915 Fax: 301-480-9290 E-mail: firstname.lastname@example.org.
Huntington’s disease (HD) is a lethal, autosomal dominant neurodegenerative disorder caused by CAG repeat expansions at exon 1 of the huntingtin (Htt) gene, which encodes for a mutant huntingtin protein (mHtt). Prominent symptoms of HD include motor dysfunction, characterized by chorea; psychiatric disturbances such as mood and personality changes; and cognitive decline that may lead to dementia. Pathologically multiple complex processes and pathways are involved in the development of HD, including selective loss of neurons in the striatum and cortex, dysregulation of cellular autophagy, mitochondrial dysfunction, decreased neurotrophic and growth factor levels, and aberrant regulation of gene expression and epigenetic patterns. No cure for HD presently exists, nor are there drugs that can halt the progression of this devastating disease. Therefore, the need to discover neuroprotective modalities to combat HD is critical. In basic and preclinical studies using cellular and animal HD models, the mood stabilizers lithium and valproic acid (VPA) have shown multiple beneficial effects, including behavioral and motor improvement, enhanced neuroprotection, and lifespan extension. Recent studies in transgenic HD mice support the notion that combined lithium/VPA treatment is more effective than treatment with either drug alone. In humans, several clinical studies of HD patients found that lithium treatment improved mood, and that VPA treatment both stabilized mood and moderately reduced chorea. In contrast, other studies observed that the hallmark features of HD were unaffected by treatment with either lithium or VPA. The current review discusses preclinical and clinical investigations of the beneficial effects of lithium and VPA on HD pathophysiology.
Huntington’s disease; Lithium; Glycogen Synthase Kinase-3 Inhibitor; Valproic Acid; Histone Deacetylase Inhibitor; Therapeutic Potential.
Date Deposited : 13 Feb 2016 11:28
Official URL: http://www.ijbs.com/v10i9
Last Modified : 13 Feb 2016 11:28
Volume 10, Number 9, - 2014 , ISSN 1449-2288
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