Study of the effect of the G2019S mutation in LRRK2: Understanding the link between peripheral inflammation and neurodegeneration in Parkinson's Disease

Identifier:  TFG:7457

Handle: https://hdl.handle.net/20.500.11797/TFG7457

Authors:  Rivas Galvez, Laia

Abstract:
Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and the accumulation of protein aggregates in the brain. This work explores the role of LRRK2 in the endolysosomal pathway, investigating how the G2019S gain-of-function mutation disrupt vesicle trafficking and protein degradation, contributing to PD pathology. Additionally, the study investigates the involvement of extracellular vesicles (EVs) in PD's inflammatory context, hypothesizing that dysfunctional lysosomal clearance of nucleic acids leads to intracellular buildup, prompting both cellular inflammation and the release of EVs. Experimental methods include EV isolation from WT and G2019S LRRK2 mutant cells, their characterization through Western blot analysis, and assessment of the inflammatory signalling pathways using pattern recognition receptor (PRR) ligands as stimulation. The findings contribute to our understanding of the interplay between LRRK2 mutations, lysosomal dysfunction, EVs, and inflammation in PD.