Modulation of cell death by alpha-synuclein is stimulus-dependent in mammalian cells.
alpha-synuclein is a neuronally-expressed protein which is mutated in familial Parkinson's disease. Previous studies have suggested that over-expression of alpha-synuclein can either enhance, reduce or have no effect on the degree of cell death in response to death-inducing stimuli. We resolve this discrepancy by using a well-characterised cell system to demonstrate that wild type alpha-synuclein can enhance cell death in response to ischaemia/reoxygenation or staurosporine treatment whilst protecting against serum removal and dopamine-induced cell death. In contrast, the two mutant forms of alpha-synuclein uniformly enhance cell death. Hence, the disease-associated mutations appear to convert alpha-synuclein from a protein which modulates cell death differently in different circumstances to forms which have a universal damaging effect.
Zourlidou
Alexandra
A
Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
Payne Smith
Martin D
MD
Latchman
David S
DS
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D051843:Synucleins; D051844:alpha-Synuclein
D016895:Culture Media, Serum-Free; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein