Synaptic phosphoproteome modifications and cortical circuit dysfunction are linked to the early-stage progression of alpha-synuclein aggregation.

ABSTRACT: Cortical dysfunction is increasingly recognized as a major contributor to the non-motor symptoms associated with Parkinson's disease (PD) and other synucleinopathies. Although functional alterations in cortical circuits have been observed in preclinical PD models, the underlying molecular mechanisms are unclear. To bridge this knowledge gap, we investigated tissue-level changes in the cortices of rats and mice treated with alpha-synuclein (aSyn) seeds using a multi-omics approach. Our study revealed significant phosphoproteomic changes, but not global proteomic or lipid profiling changes, in the rat sensorimotor cortex 3 months after intrastriatal injection with aSyn preformed fibrils (PFFs). Gene ontology analysis of the phosphoproteomic data indicated that PFF administration impacted pat

SUBMITTER: Dutta S 

PROVIDER: S-EPMC11785254 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature