Optogenetic dissection of early α-Synuclein aggregation and its molecular machinery

Abid Oueslati, PhD
Full Professor
Faculty of Medicine
Université Laval- CRCHUQ

This conference is hosted by Hideto Takahashi, PhD . This conference is part of the 2025-2026 IRCM conference calendar.

About this conference
Using optogenetic tools to precisely control the initiation of α-synuclein aggregation, we show that the earliest stages of aggregation occur at the lysosomal membrane, rather than in the bulk cytosol. These initial events are not spontaneous but require the coordinated action of aggregation-helper proteins, which act as molecular scaffolds to promote nucleation and stabilize early assemblies. Our findings identify the lysosome as a critical subcellular hub for the initiation of pathological α-synuclein and highlight aggregation-helper proteins as key regulators of this process. Together, this work reveals that early α-synuclein aggregation is spatially organized, mechanistically regulated, and potentially targetable at a stage preceding irreversible aggregate formation.

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