Understanding the contributions of VPS35 and the retromer in neurodegenerative disease.

ABSTRACT: Perturbations of the endolysosomal pathway have been suggested to play an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD). Specifically, VPS35 and the retromer complex play an important role in the endolysosomal system and are implicated in the pathophysiology of these diseases. A single missense mutation in VPS35, Asp620Asn (D620N), is known to cause late-onset, autosomal dominant familial PD. In this review, we focus on the emerging role of the PD-linked D620N mutation in causing retromer dysfunction and dissect its implications in neurodegeneration. Additionally, we will discuss how VPS35 and the retromer are linked to AD, amyotrophic lateral sclerosis, and primary tauopathies. Interestingly, reduc

SUBMITTER: Williams ET 

PROVIDER: S-EPMC9233057 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature