Why does aggregated alpha-synuclein accumulation in neurons trigger apoptosis rather than proteasomal degradation?

💡 Explanation

Aggregated alpha-synuclein overwhelms the capacity of chaperone-mediated autophagy (CMA), leading to its dysfunction and the accumulation of toxic protein aggregates; because of this buildup, the cell triggers apoptosis rather than clearing the aggregates. Therefore, impaired CMA is the cause, rather than lysosomal capacity being the primary issue.

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