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.
Ferrucci
Michela
M
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, Pisa, Italy.
Pasquali
Livia
L
Ruggieri
Stefano
S
Paparelli
Antonio
A
Fornai
Francesco
F
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology*; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein