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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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Autores principales: Lauterbach, Edward C., Fontenelle, Leonardo F., Teixeira, Antonio L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255316/
https://www.ncbi.nlm.nih.gov/pubmed/22254151
http://dx.doi.org/10.1155/2012/753548
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author Lauterbach, Edward C.
Fontenelle, Leonardo F.
Teixeira, Antonio L.
author_facet Lauterbach, Edward C.
Fontenelle, Leonardo F.
Teixeira, Antonio L.
author_sort Lauterbach, Edward C.
collection PubMed
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.
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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. Parkinsons Dis 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.
spellingShingle Review Article
Lauterbach, Edward C.
Fontenelle, Leonardo F.
Teixeira, Antonio L.
The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
title 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_short The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
title_sort neuroprotective disease-modifying potential of psychotropics in parkinson's disease
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255316/
https://www.ncbi.nlm.nih.gov/pubmed/22254151
http://dx.doi.org/10.1155/2012/753548
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