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Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects

Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson’s disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction...

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Autores principales: Borsche, Max, Pereira, Sandro L., Klein, Christine, Grünewald, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990451/
https://www.ncbi.nlm.nih.gov/pubmed/33074190
http://dx.doi.org/10.3233/JPD-201981
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author Borsche, Max
Pereira, Sandro L.
Klein, Christine
Grünewald, Anne
author_facet Borsche, Max
Pereira, Sandro L.
Klein, Christine
Grünewald, Anne
author_sort Borsche, Max
collection PubMed
description Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson’s disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction to the disease. Here, proteins encoded by the autosomal recessively inherited PD genes Parkin, PTEN-induced kinase 1 (PINK1), and DJ-1 are involved in mitochondrial pathways. Additional evidence for mitochondrial dysfunction stems from models of autosomal-dominant PD due to mutations in alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2). Moreover, patients harboring alterations in mitochondrial polymerase gamma (POLG) often exhibit signs of parkinsonism. While some molecular studies suggest that mitochondrial dysfunction is a primary event in PD, others speculate that it is the result of impaired mitochondrial clearance. Most recent research even implicated damage-associated molecular patterns released from non-degraded mitochondria in neuroinflammatory processes in PD. Here, we summarize the manifold literature dealing with mitochondria in the context of PD. Moreover, in light of recent advances in the field of personalized medicine, patient stratification according to the degree of mitochondrial impairment followed by mitochondrial enhancement therapy may hold potential for at least a subset of genetic and idiopathic PD cases. Thus, in the second part of this review, we discuss therapeutic approaches targeting mitochondrial dysfunction with the aim to prevent or delay neurodegeneration in PD.
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spelling pubmed-79904512021-04-14 Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects Borsche, Max Pereira, Sandro L. Klein, Christine Grünewald, Anne J Parkinsons Dis Review Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson’s disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction to the disease. Here, proteins encoded by the autosomal recessively inherited PD genes Parkin, PTEN-induced kinase 1 (PINK1), and DJ-1 are involved in mitochondrial pathways. Additional evidence for mitochondrial dysfunction stems from models of autosomal-dominant PD due to mutations in alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2). Moreover, patients harboring alterations in mitochondrial polymerase gamma (POLG) often exhibit signs of parkinsonism. While some molecular studies suggest that mitochondrial dysfunction is a primary event in PD, others speculate that it is the result of impaired mitochondrial clearance. Most recent research even implicated damage-associated molecular patterns released from non-degraded mitochondria in neuroinflammatory processes in PD. Here, we summarize the manifold literature dealing with mitochondria in the context of PD. Moreover, in light of recent advances in the field of personalized medicine, patient stratification according to the degree of mitochondrial impairment followed by mitochondrial enhancement therapy may hold potential for at least a subset of genetic and idiopathic PD cases. Thus, in the second part of this review, we discuss therapeutic approaches targeting mitochondrial dysfunction with the aim to prevent or delay neurodegeneration in PD. IOS Press 2021-02-02 /pmc/articles/PMC7990451/ /pubmed/33074190 http://dx.doi.org/10.3233/JPD-201981 Text en © 2021 – IOS Press. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Borsche, Max
Pereira, Sandro L.
Klein, Christine
Grünewald, Anne
Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
title Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
title_full Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
title_fullStr Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
title_full_unstemmed Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
title_short Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
title_sort mitochondria and parkinson’s disease: clinical, molecular, and translational aspects
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990451/
https://www.ncbi.nlm.nih.gov/pubmed/33074190
http://dx.doi.org/10.3233/JPD-201981
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