Background pattern of a brain with neural connections

Team Jensen

Investigate the impact of Parkinson’s disease lysosomal risk variants on lysosomal function and alpha-synuclein clearance across CNS cell types

2026-Present

Genome-wide association studies have identified 134 different loci as risk factors for Parkinson’s disease (PD), including multiple genes encoding for lysosomal proteins. However, the mechanisms by which lysosomal dysfunction contributes to PD pathogenesis remain unclear. Focusing on a targeted set of lysosomal PD risk factors (TMEM175, GBA1, GPNMB, LRRK2 and SNCA), we will determine how these variants affect lysosomal health and alpha-synuclein clearance in a cell-autonomous and noncell autonomous fashion using iPSC-derived neurons and microglia and immortalized cells lines. We will uncover the mechanistic basis by which these variants influence lysosomal homeostasis and contribute to alpha-synuclein accumulation or spreading.

Tags
Alpha-synucleinGBA (Glucocerebrosidase)GPNMBiPSC neuronsLRRK2LysosomesMicroglia

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