ClulnhForPD PROJECT

FRRB Project 1737591 - Exploring LRRK2-Clusterin pathway as a therapeutic strategy for Parkinson’s disease

PROJECT SUMMARY

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons and the presence of protein inclusions, mainly composed of a-synuclein (a-syn), in surviving neurons. The progressive neuropathological damage seen in PD is thought to be related to the neuron-to-neuron propagation of a-syn aggregated species. Thus, clearance of extracellular aggregated a-syn, mediated by glial cells and chaperones, is a key process to control a-syn propagation and PD progression. In this project, we will investigate if astrocytes carrying LRRK2 G2019S, the most common mutation of familiar and sporadic PD, display defects in clearance of a-syn mediated by the chaperone Clusterin, which could be the cause of an exacerbation a-syn propagation, neurodegeneration and behavioral abnormalities observed in LRRK2 G2019S-PD patients. Interestingly, we will explore LRRK2-Clusterin pharmacological inhibition as a therapeutic strategy to attenuate PD pathology.