Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models.

ABSTRACT:

Background

Lysosomal dysfunction has been implicated in a number of neurodegenerative diseases such as Parkinson's disease (PD). Various molecular, clinical and genetic studies have highlighted a central role of lysosomal pathways and proteins in the pathogenesis of PD. Within PD pathology the synaptic protein alpha-synuclein (αSyn) converts from a soluble monomer to oligomeric structures and insoluble amyloid fibrils. The aim of this study was to unravel the effect of αSyn aggregates on lysosomal turnover, particularly focusing on lysosomal homeostasis and cathepsins. Since these enzymes have been shown to be directly involved in the lysosomal degradation of αSyn, impairment of their enzymatic capacity has extensive consequences.

Methods

We used patient-derived induced plur

SUBMITTER: Drobny A 

PROVIDER: S-EPMC10262594 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature