In:
Brain, Oxford University Press (OUP), Vol. 145, No. 12 ( 2022-12-19), p. 4349-4367
Kurzfassung:
Parkinson’s disease is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies has considerably advanced our understanding of the Parkinson’s disease genetic risk. Understanding the functional significance of the risk loci is now a critical step towards translating these genetic advances into an enhanced biological understanding of the disease. Impaired mitophagy is a key causative pathway in familial Parkinson’s disease, but its relevance to idiopathic Parkinson’s disease is unclear. We used a mitophagy screening assay to evaluate the functional significance of risk genes identified through genome-wide association studies. We identified two new regulators of PINK1-dependent mitophagy initiation, KAT8 and KANSL1, previously shown to modulate lysine acetylation. These findings suggest PINK1-mitophagy is a contributing factor to idiopathic Parkinson’s disease. KANSL1 is located on chromosome 17q21 where the risk associated gene has long been considered to be MAPT. While our data do not exclude a possible association between the MAPT gene and Parkinson’s disease, they provide strong evidence that KANSL1 plays a crucial role in the disease. Finally, these results enrich our understanding of physiological events regulating mitophagy and establish a novel pathway for drug targeting in neurodegeneration.
Materialart:
Online-Ressource
ISSN:
0006-8950
,
1460-2156
DOI:
10.1093/brain/awac325
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2022
ZDB Id:
1474117-9
SSG:
12
