Inactivation mechanism of alpha-synuclein oligomer toxicity in Parkinson's disease

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In our study, we investigate how neurons counteract the harmful effects of toxic α-synuclein oligomers in Parkinson's disease. The accumulation of these oligomers, which occurs due to excessive α-synuclein levels in cells, is associated with neuronal death and disease progression. Our research has uncovered that lysosomal degradation and the formation of aggresomes play a crucial role in preventing the formation and neutralizing the toxicity of these oligomers in neurons. We identified that these processes are co-regulated by three proteins: USP10, G3BP1, and p62. We discovered USP10 activity to regulate selective degradation of α-synuclein, as well as potentially other disease-related proteins through shared mechanism.