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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/4/3264 |
| _version_ | 1797620635401191424 |
|---|---|
| author | Isaac Pérez-Segura Alberto Santiago-Balmaseda Luis Daniel Rodríguez-Hernández Adriana Morales-Martínez Hilda Angélica Martínez-Becerril Paola A. Martínez-Gómez Karen M. Delgado-Minjares Citlaltepetl Salinas-Lara Irma A. Martínez-Dávila Magdalena Guerra-Crespo Francisca Pérez-Severiano Luis O. Soto-Rojas |
| author_facet | Isaac Pérez-Segura Alberto Santiago-Balmaseda Luis Daniel Rodríguez-Hernández Adriana Morales-Martínez Hilda Angélica Martínez-Becerril Paola A. Martínez-Gómez Karen M. Delgado-Minjares Citlaltepetl Salinas-Lara Irma A. Martínez-Dávila Magdalena Guerra-Crespo Francisca Pérez-Severiano Luis O. Soto-Rojas |
| author_sort | Isaac Pérez-Segura |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T08:44:25Z |
| format | Article |
| id | doaj.art-dbdc72cb1f004600b29e6c36be6f3aba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:44:25Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dbdc72cb1f004600b29e6c36be6f3aba2023-11-16T20:57:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244326410.3390/ijms24043264PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy?Isaac Pérez-Segura0Alberto Santiago-Balmaseda1Luis Daniel Rodríguez-Hernández2Adriana Morales-Martínez3Hilda Angélica Martínez-Becerril4Paola A. Martínez-Gómez5Karen M. Delgado-Minjares6Citlaltepetl Salinas-Lara7Irma A. Martínez-Dávila8Magdalena Guerra-Crespo9Francisca Pérez-Severiano10Luis O. Soto-Rojas11Laboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Medicina Regenerativa, Facultad de Medicina, Departamento de Fisiología, Universidad Nacional Autónoma de México, Mexico City 04360, MexicoLaboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City 07360, MexicoLaboratorio de Medicina Regenerativa, Facultad de Medicina, Departamento de Fisiología, Universidad Nacional Autónoma de México, Mexico City 04360, MexicoLaboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, MexicoLaboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoParkinson’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.https://www.mdpi.com/1422-0067/24/4/3264α-synucleinopathyneuroprotectionParkinson’s diseaseLewy bodiesPPARglitazones |
| spellingShingle | Isaac Pérez-Segura Alberto Santiago-Balmaseda Luis Daniel Rodríguez-Hernández Adriana Morales-Martínez Hilda Angélica Martínez-Becerril Paola A. Martínez-Gómez Karen M. Delgado-Minjares Citlaltepetl Salinas-Lara Irma A. Martínez-Dávila Magdalena Guerra-Crespo Francisca Pérez-Severiano Luis O. Soto-Rojas PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? International Journal of Molecular Sciences α-synucleinopathy neuroprotection Parkinson’s disease Lewy bodies PPAR glitazones |
| 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 | α-synucleinopathy neuroprotection Parkinson’s disease Lewy bodies PPAR glitazones |
| url | https://www.mdpi.com/1422-0067/24/4/3264 |
| work_keys_str_mv | AT isaacperezsegura pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT albertosantiagobalmaseda pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT luisdanielrodriguezhernandez pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT adrianamoralesmartinez pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT hildaangelicamartinezbecerril pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT paolaamartinezgomez pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT karenmdelgadominjares pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT citlaltepetlsalinaslara pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT irmaamartinezdavila pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT magdalenaguerracrespo pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT franciscaperezseveriano pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy AT luisosotorojas pparsandtheirneuroprotectiveeffectsinparkinsonsdiseaseanoveltherapeuticapproachinasynucleinopathy |