Parkin Beyond Parkinson's Disease-A Functional Meaning of Parkin Downregulation in TDP-43 Proteinopathies

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Dec 24

PMID 34943897

Citations 4

Authors

Katarzyna Gaweda-Walerych

Emilia Jadwiga Sitek

Ewa Narozanska

Emanuele Buratti

Affiliations

Soon will be listed here.

Abstract

Parkin and PINK1 are key regulators of mitophagy, an autophagic pathway for selective elimination of dysfunctional mitochondria. To this date, parkin depletion has been associated with recessive early onset Parkinson's disease (PD) caused by loss-of-function mutations in the gene, while, in sporadic PD, the activity and abundance of this protein can be compromised by stress-related modifications. Intriguingly, research in recent years has shown that parkin depletion is not limited to PD but is also observed in other neurodegenerative diseases-especially those characterized by TDP-43 proteinopathies, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here, we discuss the evidence of parkin downregulation in these disease phenotypes, its emerging connections with TDP-43, and its possible functional implications.

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