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- W3174404738 abstract "Mn-containing dithiocarbamates, such as maneb (MB) and mancozeb (MZ), have been known to increase the toxicity of neurotoxin MPTP on dopaminergic neurons leading to cell death and Parkinson-like symptoms. Dopamine transporter (DAT), a key protein in MPTP's toxicity, transports the active metabolite (MPP+) into dopaminergic neurons; increasing the cell surface expression of DAT increases uptake of MPTP. Alpha-synuclein (both wt and A30P & A53T mutants) have been associated with Parkinson's, and are thought to regulate DAT trafficking by interacting with DAT. The aim of this study is elucidate the role of the alpha-synuclein and its mutants on dithiocarbamate cytotoxicity. HEK cells transfected with DAT and alpha-synuclein (either wt or mutant) were treated with dithiocarbamates. Lysates were used for co-immunoprecipitation using anti-DAT antibody. The precipitated proteins were subjected to Western blot analysis using alpha-synuclein and DAT antibodies. We report roughly a 30% decrease in the DAT/alpha-synuclein interaction in the presence of the A53T mutant versus wild-type, but not in the present of A30P mutant. With dithiocarbamates the interaction of DAT and alpha-synuclein (wt) was enhanced, with increases ranging from 50% to 200%. Pesticide treated A53T mutants respond more dramatically than A30P mutants in increasing the interaction between the DAT and the alpha-synuclein." @default.
- W3174404738 created "2021-07-05" @default.
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- W3174404738 date "2012-04-01" @default.
- W3174404738 modified "2023-09-27" @default.
- W3174404738 title "Role of Alpha‐Synuclein and it mutants on Dithiocarbamates Cytotoxicity" @default.
- W3174404738 doi "https://doi.org/10.1096/fasebj.26.1_supplement.lb228" @default.
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