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PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy?
Parkinson’s disease (PD) is the most common α-synucleinopathy worldwide. The pathognomonic hallmark of PD is the misfolding and propagation of the α-synuclein (α-syn) protein, observed in post-mortem histopathology. It has been hypothesized that α-synucleinopathy triggers oxidative stress, mitochond...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963164/ https://www.ncbi.nlm.nih.gov/pubmed/36834679 http://dx.doi.org/10.3390/ijms24043264 |
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author | Pérez-Segura, Isaac Santiago-Balmaseda, Alberto Rodríguez-Hernández, Luis Daniel Morales-Martínez, Adriana Martínez-Becerril, Hilda Angélica Martínez-Gómez, Paola A. Delgado-Minjares, Karen M. Salinas-Lara, Citlaltepetl Martínez-Dávila, Irma A. Guerra-Crespo, Magdalena Pérez-Severiano, Francisca Soto-Rojas, Luis O. |
author_facet | Pérez-Segura, Isaac Santiago-Balmaseda, Alberto Rodríguez-Hernández, Luis Daniel Morales-Martínez, Adriana Martínez-Becerril, Hilda Angélica Martínez-Gómez, Paola A. Delgado-Minjares, Karen M. Salinas-Lara, Citlaltepetl Martínez-Dávila, Irma A. Guerra-Crespo, Magdalena Pérez-Severiano, Francisca Soto-Rojas, Luis O. |
author_sort | Pérez-Segura, Isaac |
collection | PubMed |
description | Parkinson’s disease (PD) is the most common α-synucleinopathy worldwide. The pathognomonic hallmark of PD is the misfolding and propagation of the α-synuclein (α-syn) protein, observed in post-mortem histopathology. It has been hypothesized that α-synucleinopathy triggers oxidative stress, mitochondrial dysfunction, neuroinflammation, and synaptic dysfunction, leading to neurodegeneration. To this date, there are no disease-modifying drugs that generate neuroprotection against these neuropathological events and especially against α-synucleinopathy. Growing evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists confer neuroprotective effects in PD, however, whether they also confer an anti-α-synucleinopathy effect is unknown. Here we analyze the reported therapeutic effects of PPARs, specifically the gamma isoform (PPARγ), in preclinical PD animal models and clinical trials for PD, and we suggest possible anti-α-synucleinopathy mechanisms acting downstream from these receptors. Elucidating the neuroprotective mechanisms of PPARs through preclinical models that mimic PD as closely as possible will facilitate the execution of better clinical trials for disease-modifying drugs in PD. |
format | Online Article Text |
id | pubmed-9963164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99631642023-02-26 PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? Pérez-Segura, Isaac Santiago-Balmaseda, Alberto Rodríguez-Hernández, Luis Daniel Morales-Martínez, Adriana Martínez-Becerril, Hilda Angélica Martínez-Gómez, Paola A. Delgado-Minjares, Karen M. Salinas-Lara, Citlaltepetl Martínez-Dávila, Irma A. Guerra-Crespo, Magdalena Pérez-Severiano, Francisca Soto-Rojas, Luis O. Int J Mol Sci Review Parkinson’s disease (PD) is the most common α-synucleinopathy worldwide. The pathognomonic hallmark of PD is the misfolding and propagation of the α-synuclein (α-syn) protein, observed in post-mortem histopathology. It has been hypothesized that α-synucleinopathy triggers oxidative stress, mitochondrial dysfunction, neuroinflammation, and synaptic dysfunction, leading to neurodegeneration. To this date, there are no disease-modifying drugs that generate neuroprotection against these neuropathological events and especially against α-synucleinopathy. Growing evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists confer neuroprotective effects in PD, however, whether they also confer an anti-α-synucleinopathy effect is unknown. Here we analyze the reported therapeutic effects of PPARs, specifically the gamma isoform (PPARγ), in preclinical PD animal models and clinical trials for PD, and we suggest possible anti-α-synucleinopathy mechanisms acting downstream from these receptors. Elucidating the neuroprotective mechanisms of PPARs through preclinical models that mimic PD as closely as possible will facilitate the execution of better clinical trials for disease-modifying drugs in PD. MDPI 2023-02-07 /pmc/articles/PMC9963164/ /pubmed/36834679 http://dx.doi.org/10.3390/ijms24043264 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Pérez-Segura, Isaac Santiago-Balmaseda, Alberto Rodríguez-Hernández, Luis Daniel Morales-Martínez, Adriana Martínez-Becerril, Hilda Angélica Martínez-Gómez, Paola A. Delgado-Minjares, Karen M. Salinas-Lara, Citlaltepetl Martínez-Dávila, Irma A. Guerra-Crespo, Magdalena Pérez-Severiano, Francisca Soto-Rojas, Luis O. PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? |
title | PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? |
title_full | PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? |
title_fullStr | PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? |
title_full_unstemmed | PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? |
title_short | PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? |
title_sort | ppars and their neuroprotective effects in parkinson’s disease: a novel therapeutic approach in α-synucleinopathy? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963164/ https://www.ncbi.nlm.nih.gov/pubmed/36834679 http://dx.doi.org/10.3390/ijms24043264 |
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