Preprint: WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease
WHY IT MATTERS
Understanding exactly where and how alpha-synuclein clumping begins could lead to new Parkinson's treatments that stop the process at its earliest stage, potentially slowing or preventing neuronal damage before symptoms appear.
Scientists discovered that a protein called WDR44 helps trigger the clumping of another protein called alpha-synuclein inside brain cells, specifically at structures called lysosomes (which are like the cell's trash cans). This clumping is what causes Parkinson's disease. By watching this process happen in real-time in living neurons, researchers got a clearer picture of how the disease starts.
WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease Authors: Teixeira, M. et al. Server: bioRxiv Category: neuroscience Abstract: The aggregation of -synuclein (-SYN) into Lewy bodies (LBs) is a central event in the pathogenesis of Parkinsons disease (PD) and related synucleinopathies1,2. Despite significant advances in understanding -SYN self-assembly, the precise sequence of early aggregation steps has not been directly visualized in living neurons. Here, we use an optogenetic-induced protein aggregation system with a high temporal resolution to monitor the onset of -SYN assembly in neurons. We found that the initiation and accumulation of -SYN aggregates occur predominantly at the lysosomal membrane, an event driven b