Alpha-synuclein and autophagy as common steps in neurodegeneration

The major component of Lewy bodies in Parkinson's disease (PD) is alpha-synuclein, which is considered as a substrate of the ubiquitin-proteasome (UP) system, although autophagy seems to be equally involved. Here we discuss the co-existence of alpha-synuclein and proteins belonging to the UP system within autophagic granules, further developing as neuronal inclusions. We hypothesize that, following slight insults, both UP and autophagy are induced; if toxic stimuli are prolonged, these pathways are overwhelmed and cell death occurs. We then indicate a protective role of autophagy in PD and suggest it as a therapeutic target to slow down the progression of the disease.