Brain Mitochondria, Aging, and Parkinson's Disease

Genes
Mario Rango, Nereo Bresolin

Abstract

This paper reconsiders the role of mitochondria in aging and in Parkinson's Disease (PD). The most important risk factor for PD is aging. Alterations in mitochondrial activity are typical of aging. Mitochondrial aging is characterized by decreased oxidative phosphorylation, proteasome activity decrease, altered autophagy, and mitochondrial dysfunction. Beyond declined oxidative phosphorylation, mitochondrial dysfunction consists of a decline of beta-oxidation as well as of the Krebs cycle. Not inherited mitochondrial DNA (mtDNA) mutations are acquired over time and parallel the decrease in oxidative phosphorylation. Many of these mitochondrial alterations are also found in the PD brain specifically in the substantia nigra (SN). mtDNA deletions and development of respiratory chain deficiency in SN neurons of aged individuals as well as of individuals with PD converge towards a shared pathway, which leads to neuronal dysfunction and death. Finally, several nuclear genes that are mutated in hereditary PD are usually implicated in mitochondrial functioning to a various extent and their mutation may cause mitochondrial impairment. In conclusion, a tight link exists between mitochondria, aging, and PD.

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Citations

Jul 8, 2020·Journal of Neuroscience Research·Vania Macías-CalvioMaría-Paz Marzolo
Jan 9, 2019·Frontiers in Pharmacology·Jhana O HendrickxStuart Maudsley
Oct 26, 2018·CPT: Pharmacometrics & Systems Pharmacology·Suruchi BakshiPiet H van der Graaf
May 15, 2020·Scientific Reports·Yukako NakagamiKosaku Murakami
May 24, 2020·Molecular Neurobiology·Giacomo Monzio CompagnoniEliezer Masliah
Jul 22, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Marco MalagutiSilvana Hrelia
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Tsu-Kung LinTzu-Jou Wang
Nov 17, 2020·Frontiers in Physiology·Sakdithep Chaiyarit, Visith Thongboonkerd
Mar 19, 2021·Frontiers in Aging Neuroscience·Ewa SikoraJakub Wlodarczyk
Apr 21, 2021·Expert Review of Proteomics·Morteza AbyadehMehdi Mirzaei
Jun 15, 2021·ACS Chemical Neuroscience·Prabitha PB R Prashantha Kumar

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