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Team Pfeffer
Convergent Mechanisms of LRRK2 and GBA in PD: vulnerability of lysosomes and neuroprotective ciliary signaling
Our recent work points to convergent pathways for the mechanisms by which LRRK2, GBA1, PINK1 and SNCA mutations are linked to PD. We propose to investigate pathway convergence by comparing the consequences of LRRK2, GBA1, and SNCA mutations in lysosomal stress and Hedgehog signaling pathways in mouse and human brain. We focus on cell type-specific vulnerability across brain regions implicated in non-motor symptoms: the PPN and piriform cortex. We hypothesize that loss of Hedgehog signaling contributes to both motor and non-motor PD symptoms. We will also develop the first PD relevant proteomic, lipidomic and phospho-lysosome atlas for human brain and blood.
Tags
Cell biologyCiliogenesisEndolysosomal dysfunctionGBA (Glucocerebrosidase)LRRK2 pathwayLysosomal dysfunctionNeuroprotective/regenerativeRab GTPases
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