title: A loss in cellular protein partners promotes α-synuclein aggregation in cells resulting from oxidative stress.
abstract: There is a consensus that oxidative stress promotes neurodegeneration and may be linked to plaque formation. α-Synuclein is the main component of neurodegenerative plaques. We have found that α-synuclein binds strongly to the enzyme phospholipase Cβ1 (PLCβ1) in vitro and in cells affecting both its G protein activation and its degradation. Because PLCβ1 binds to α-synuclein in cells, we tested whether decreasing its level would promote α-synuclein aggregation and whether overproducing PLCβ1 would inhibit aggregation. By imaging fluorescent α-synuclein in living HEK293, PC12, and SK-H-SH cells, we find that α-synuclein aggregation is directly related to the level of PLCβ1. Importantly, we found that oxidative stress does not affect the cellular levels of α-synuclein but results in the down-regulation of PLCβ1 thereby promoting α-synuclein aggregation. A peptide that mimics part of the α-synuclein binding site to PLCβ prevents aggregation. Our studies indicate that PLCβ1 can reduce cell damage under oxidative stress and offers a potential site that might be exploited to prevent α-synuclein aggregation.
authors: Department of Physiology & Biophysics, Stony Brook University, Stony Brook, New York 11794-8661, United States.
authors: Yuanjian
authors: Y
authors: Guo
authors: Suzanne
authors: S
authors: Scarlata
mesh_terms: D000818:Animals; D001665:Binding Sites; D015536:Down-Regulation; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D054799:Phospholipase C beta / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D051844:alpha-Synuclein; D054799:Phospholipase C beta
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