Is Disrupted Mitophagy a Central Player to Parkinson's Disease Pathology?
lewy body
mitophagy
parkin
parkinson's disease
pink1
Journal
Cureus
ISSN: 2168-8184
Titre abrégé: Cureus
Pays: United States
ID NLM: 101596737
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
accepted:
25
02
2023
entrez:
2
3
2023
pubmed:
3
3
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Whilst the pathophysiology at a cellular level has been defined, the cause of Parkinson's disease (PD) remains poorly understood. This neurodegenerative disorder is associated with impaired dopamine transmission in the substantia nigra, and protein accumulations known as Lewy bodies are visible in affected neurons. Cell culture models of PD have indicated impaired mitochondrial function, so the focus of this paper is on the quality control processes involved in and around mitochondria. Mitochondrial autophagy (mitophagy) is the process through which defective mitochondria are removed from the cell by internalisation into autophagosomes which fuse with a lysosome. This process involves many proteins, notably including PINK1 and parkin, both of which are known to be coded on genes associated with PD. Normally in healthy individuals, PINK1 associates with the outer mitochondrial membrane, which then recruits parkin, activating it to attach ubiquitin proteins to the mitochondrial membrane. PINK1, parkin, and ubiquitin cooperate to form a positive feedback system which accelerates the deposition of ubiquitin on dysfunctional mitochondria, resulting in mitophagy. However, in hereditary PD, the genes encoding PINK1 and parkin are mutated, resulting in proteins that are less efficient at removing poorly performing mitochondria, leaving cells more vulnerable to oxidative stress and ubiquitinated inclusion bodies, such as Lewy bodies. Current research that looks into the connection between mitophagy and PD is promising, already yielding potentially therapeutic compounds; until now, pharmacological support for the mitophagy process has not been part of the therapeutic arsenal. Continued research in this area is warranted.
Identifiants
pubmed: 36860818
doi: 10.7759/cureus.35458
pmc: PMC9969326
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
e35458Informations de copyright
Copyright © 2023, Ko et al.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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