Alpha-synuclein's degradation in vivo: opening a new (cranial) window on the roles of degradation pathways in Parkinson disease.
Progressive accumulation of α-synuclein is key to the pathology of many neurodegenerative diseases, including Parkinson disease and dementia with Lewy bodies. Increased intracellular levels of α-synuclein may be caused by enhanced expression or alterations in protein degradation pathways. Here we review our recent study showing that the ubiquitin-proteasome system and the autophagy-lysosomal pathway are differentially involved in α-synuclein's degradation in vivo. We discuss the key findings obtained with our novel in vivo approach and also present a model for the progression of protein aggregation and dysfunctional degradation in Parkinson disease.
MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Darius
D
Ebrahimi-Fakhari
Pamela J
PJ
McLean
Vivek K
VK
Unni
D000818:Animals; D001343:Autophagy; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D010588:Phagosomes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
D025801:Ubiquitin; D051844:alpha-Synuclein; D046988:Proteasome Endopeptidase Complex