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Int. J. Mol. Sci. 2013, 14(11), 22558-22603; doi:10.3390/ijms141122558
Review

Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease

1,2,3
1 Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, 655 First Street, Macon, GA 31201, USA 2 Department of Internal Medicine, Neurology Section, Mercer University School of Medicine, 707 Pine Street, Macon, GA 31201, USA 3 Center for Translational Studies In Neurodegenerative Disease, Mercer University, 1400 Coleman Avenue, Macon, GA 31207, USA 
Received: 19 August 2013 / Revised: 16 October 2013 / Accepted: 16 October 2013 / Published: 15 November 2013
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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Abstract

Psychotropics (antipsychotics, mood stabilizers, antidepressants, anxiolytics, etc.) are commonly prescribed to treat Huntington’s disease (HD). In HD preclinical models, while no psychotropic has convincingly affected huntingtin gene, HD modifying gene, or huntingtin protein expression, psychotropic neuroprotective effects include upregulated huntingtin autophagy (lithium), histone acetylation (lithium, valproate, lamotrigine), miR-222 (lithium-plus-valproate), mitochondrial protection (haloperidol, trifluoperazine, imipramine, desipramine, nortriptyline, maprotiline, trazodone, sertraline, venlafaxine, melatonin), neurogenesis (lithium, valproate, fluoxetine, sertraline), and BDNF (lithium, valproate, sertraline) and downregulated AP-1 DNA binding (lithium), p53 (lithium), huntingtin aggregation (antipsychotics, lithium), and apoptosis (trifluoperazine, loxapine, lithium, desipramine, nortriptyline, maprotiline, cyproheptadine, melatonin). In HD live mouse models, delayed disease onset (nortriptyline, melatonin), striatal preservation (haloperidol, tetrabenazine, lithium, sertraline), memory preservation (imipramine, trazodone, fluoxetine, sertraline, venlafaxine), motor improvement (tetrabenazine, lithium, valproate, imipramine, nortriptyline, trazodone, sertraline, venlafaxine), and extended survival (lithium, valproate, sertraline, melatonin) have been documented. Upregulated CREB binding protein (CBP; valproate, dextromethorphan) and downregulated histone deacetylase (HDAC; valproate) await demonstration in HD models. Most preclinical findings await replication and their limitations are reviewed. The most promising findings involve replicated striatal neuroprotection and phenotypic disease modification in transgenic mice for tetrabenazine and for sertraline. Clinical data consist of an uncontrolled lithium case series (n = 3) suggesting non-progression and a primarily negative double-blind, placebo-controlled clinical trial of lamotrigine.
Keywords: neurodegenerative disease; antipsychotic; mood stabilizer; antidepressant; anxiolytic; hypnotic; gene expression; epigenetics; apoptosis; animal model; Huntington’s disease neurodegenerative disease; antipsychotic; mood stabilizer; antidepressant; anxiolytic; hypnotic; gene expression; epigenetics; apoptosis; animal model; Huntington’s disease
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Lauterbach, E.C. Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease. Int. J. Mol. Sci. 2013, 14, 22558-22603.

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