α-Synuclein Is Degraded by Both Autophagy and the Proteasome

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of aggregates (Lewy bodies) in neurons. α-Synuclein is the major protein in Lewy bodies and rare mutations in α-synuclein cause early-onset PD. Consequently, α-synuclein is implicated in the pathogenesis of PD. Here, we have investigated the degradation pathways of α-synuclein, using a stable inducible PC12 cell model, where the expression of exogenous human wild-type, A30P, or A53T α-synuclein can be switched on and off. We have used a panel of inhibitors/stimulators of autophagy and proteasome function and followed α-synuclein degradation in these cells. We found that not only is…

• WT
  Wellcome Trust
• PU
  Parkinson's UK