The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

Neuroprotective treatments in Parkinson's disease (PD) have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial funct...

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Main Authors:	Lauterbach, Edward C., Fontenelle, Leonardo F., Teixeira, Antonio L.
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255316/

id	pubmed-3255316
recordtype	oai_dc
spelling	pubmed-32553162012-01-17 The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease Lauterbach, Edward C. Fontenelle, Leonardo F. Teixeira, Antonio L. Review Article Neuroprotective treatments in Parkinson's disease (PD) have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms) include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R), although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS), reactive nitrogen species (RNS), apoptosis, inflammation, and trophic factors including GDNF and BDNF. Hindawi Publishing Corporation 2012 2011-12-27 /pmc/articles/PMC3255316/ /pubmed/22254151 http://dx.doi.org/10.1155/2012/753548 Text en Copyright © 2012 Edward C. Lauterbach et al. https://creativecommons.org/licenses/by/3.0/ 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lauterbach, Edward C. Fontenelle, Leonardo F. Teixeira, Antonio L.
spellingShingle	Lauterbach, Edward C. Fontenelle, Leonardo F. Teixeira, Antonio L. The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
author_facet	Lauterbach, Edward C. Fontenelle, Leonardo F. Teixeira, Antonio L.
author_sort	Lauterbach, Edward C.
title	The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
title_short	The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
title_full	The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
title_fullStr	The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
title_full_unstemmed	The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
title_sort	neuroprotective disease-modifying potential of psychotropics in parkinson's disease
description	Neuroprotective treatments in Parkinson's disease (PD) have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms) include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R), although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS), reactive nitrogen species (RNS), apoptosis, inflammation, and trophic factors including GDNF and BDNF.
publisher	Hindawi Publishing Corporation
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255316/
_version_	1611499245460783104

The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

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