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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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2012/753548 |
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| author | Edward C. Lauterbach Leonardo F. Fontenelle Antonio L. Teixeira |
| author_facet | Edward C. Lauterbach Leonardo F. Fontenelle Antonio L. Teixeira |
| author_sort | Edward C. Lauterbach |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-9153a4268a764211821ddda32c628578 |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-9153a4268a764211821ddda32c6285782025-02-03T01:25:37ZengWileyParkinson's Disease2090-80832042-00802012-01-01201210.1155/2012/753548753548The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's DiseaseEdward C. Lauterbach0Leonardo F. Fontenelle1Antonio L. Teixeira2Department of Psychiatry and Behavioral Sciences and the Department of Internal Medicine, Neurology Section, Mercer University School of Medicine, 1400 Coleman Avenue, Macon, GA 31201, USAAnxiety and Depression Research Program, Institute of Psychiatry, Federal University of Rio de Janeiro (IPUB/UFRJ), CEP: 22290-140 Rio de Janeiro, RJ, BrazilNeurology Group, Department of Internal Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, BrazilNeuroprotective 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.http://dx.doi.org/10.1155/2012/753548 |
| spellingShingle | Edward C. Lauterbach Leonardo F. Fontenelle Antonio L. Teixeira The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease 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 |
| url | http://dx.doi.org/10.1155/2012/753548 |
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