Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease
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, psychotropi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2013-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/14/11/22558 |
| _version_ | 1811299231996051456 |
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| author | Edward C. Lauterbach |
| author_facet | Edward C. Lauterbach |
| author_sort | Edward C. Lauterbach |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T06:33:09Z |
| publishDate | 2013-11-01 |
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| spelling | doaj.art-a66e23eb1b234874a8dcc08fff5c32e42022-12-22T02:58:03ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-11-011411225582260310.3390/ijms141122558Neuroprotective Effects of Psychotropic Drugs in Huntington’s DiseaseEdward C. LauterbachPsychotropics (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.http://www.mdpi.com/1422-0067/14/11/22558neurodegenerative diseaseantipsychoticmood stabilizerantidepressantanxiolytichypnoticgene expressionepigeneticsapoptosisanimal modelHuntington’s disease |
| spellingShingle | Edward C. Lauterbach Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease International Journal of Molecular Sciences neurodegenerative disease antipsychotic mood stabilizer antidepressant anxiolytic hypnotic gene expression epigenetics apoptosis animal model Huntington’s disease |
| title | Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease |
| title_full | Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease |
| title_fullStr | Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease |
| title_full_unstemmed | Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease |
| title_short | Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease |
| title_sort | neuroprotective effects of psychotropic drugs in huntington s disease |
| topic | neurodegenerative disease antipsychotic mood stabilizer antidepressant anxiolytic hypnotic gene expression epigenetics apoptosis animal model Huntington’s disease |
| url | http://www.mdpi.com/1422-0067/14/11/22558 |
| work_keys_str_mv | AT edwardclauterbach neuroprotectiveeffectsofpsychotropicdrugsinhuntingtonsdisease |