Why does aggregated alpha-synuclein in Parkinson's disease trigger neuronal death via the ubiquitin-proteasome system (UPS)?

💡 Explanation

Aggregated alpha-synuclein impairs the ubiquitin-proteasome system because the aggregates accumulate faster than the UPS can clear them, therefore leading to proteotoxic stress and neuronal death, rather than direct mitochondrial targeting, enhanced proteasome activity or upregulation of chaperones that would help mitigate the aggregate.

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