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- W2090870097 abstract "Microglial neuroinflammatory responses affect the onset and progression of Parkinson's disease (PD). We posit that such neuroinflammatory responses are, in part, mediated by microglial interactions with nitrated and aggregated alpha-synuclein (alpha-syn) released from Lewy bodies as a consequence of dopaminergic neuronal degeneration. As disease progresses, secretions from alpha-syn-activated microglia can engage neighboring glial cells in a cycle of autocrine and paracrine amplification of neurotoxic immune products. Such pathogenic processes affect the balance between a microglial neurotrophic and neurotoxic signature. We now report that microglia secrete both neurotoxic and neuroprotective factors after exposure to nitrated alpha-syn (N-alpha-syn). Proteomic (surface enhanced laser desorption-time of flight, 1D sodium dodecyl sulfate electrophoresis, and liquid chromatography-tandem mass spectrometry) and limited metabolomic profiling demonstrated that N-alpha-syn-activated microglia secrete inflammatory, regulatory, redox-active, enzymatic, and cytoskeletal proteins. Increased extracellular glutamate and cysteine and diminished intracellular glutathione and secreted exosomal proteins were also demonstrated. Increased redox-active proteins suggest regulatory microglial responses to N-alpha-syn. These were linked to discontinuous cystatin expression, cathepsin activity, and nuclear factor-kappa B activation. Inhibition of cathepsin B attenuated, in part, N-alpha-syn microglial neurotoxicity. These data support multifaceted microglia functions in PD-associated neurodegeneration." @default.
- W2090870097 created "2016-06-24" @default.
- W2090870097 creator A5008473098 @default.
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- W2090870097 date "2008-01-17" @default.
- W2090870097 modified "2023-10-06" @default.
- W2090870097 title "Nitrated Alpha-Synuclein and Microglial Neuroregulatory Activities" @default.
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- W2090870097 doi "https://doi.org/10.1007/s11481-008-9100-z" @default.
- W2090870097 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2430927" @default.
- W2090870097 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18202920" @default.
- W2090870097 hasPublicationYear "2008" @default.
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