Parkin beyond Parkinson’s Disease—A Functional Meaning of Parkin Downregulation in TDP-43 Proteinopathies

Cells

Katarzyna Gaweda-Walerych¹  Emanuele Buratti²  Ewa Narożańska³  Emilia Jadwiga Sitek³ 

[1] Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;Molecular Pathology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), AREA Science Park, 34149 Trieste, Italy;Neurology Department, St. Adalbert Hospital, Copernicus PL, 80-462 Gdansk, Poland;

关键词: TDP-43 pathology;    parkin;    mitophagy;    fronto-temporal lobar degeneration (FTLD);    amyotrophic lateral sclerosis (ALS);    Parkinson’s disease (PD);   

DOI  :  10.3390/cells10123389

来源: DOAJ

【 摘 要 】

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 PARK2 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.

【 授权许可】

Unknown