Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system

Bhore, N; Bogacki, EC; OCallaghan, B; Plun-Favreau, H; Lewis, PA; Herbst, S

Abstract

Parkinson's disease is a progressive neurological disorder, characterized by prominent movement dysfunction. The past two decades have seen a rapid expansion of our understanding of the genetic basis of Parkinson's, initially through the identification of monogenic forms and, more recently, through genome-wide association studies identifying common risk variants. Intriguingly, a number of cellular pathways have emerged from these analysis as playing central roles in the aetiopathogenesis of Parkinson's. In this review, the impact of data deriving from genome-wide analyses for Parkinson's upon our functional understanding of the disease will be examined, with a particular focus on examples of endo-lysosomal and mitochondrial dysfunction. The challenges of moving from a genetic to a functional understanding of common risk variants for Parkinson's will be discussed, with a final consideration of the current state of the genetic architecture of the disorder.This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.

Citation

Bhore, N., Bogacki, E., OCallaghan, B., Plun-Favreau, H., Lewis, P., & Herbst, S. (2024). Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system. Philosophical Transactions of the Royal Society B: Biological Sciences, 379(1899), https://doi.org/10.1098/rstb.2022.0517

• Journal Article Type: Article
• Acceptance Date: Oct 18, 2023
• Online Publication Date: Feb 19, 2024
• Publication Date: 2024
• Deposit Date: Apr 15, 2024
• Publicly Available Date: Apr 15, 2024
• Journal: Philosophical Transactions of the Royal Society B: Biological Sciences
• Print ISSN: 0962-8436
• Electronic ISSN: 1471-2970
• Publisher: The Royal Society
• Peer Reviewed: Peer Reviewed
• Volume: 379
• Issue: 1899
• DOI: https://doi.org/10.1098/rstb.2022.0517
• Keywords: Parkinson's disease; genome-wide association; functional genomics; endo-lysosomal; GENOME-WIDE ASSOCIATION; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; THERAPEUTIC TARGET; EMERGING ROLE; METAANALYSIS; UBIQUITIN; DEMENTIA; IDENTIFICATION; ARCHITECTURE