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- W4308590804 abstract "The unique thermodynamic and kinetic coordination chemistry of ruthenium allows it to modulate key adverse aggregation and membrane interactions of α-synuclein (α-syn) associated with Parkinson’s disease. We show that the low-toxic Ru(III) complex trans-[ImH][RuCl4(Me2SO)(Im)] (NAMI-A) has dual inhibitory effects on both aggregation and membrane interactions of α-syn with submicromolar affinity, and disassembles pre-formed fibrils. NAMI-A abolishes the cytotoxicity of α-syn towards neuronal cells and mitigates neurodegeneration and motor impairments in a rat model of Parkinson's. Multinuclear NMR and MS analyses show that NAMI-A binds to residues involved in protein aggregation and membrane binding. NMR studies reveal the key steps in pro-drug activation and the effect of activated NAMI-A species on protein folding. Our findings provide a new basis for designing ruthenium complexes which could mitigate α-syn-induced Parkinson's pathology differently from organic agents." @default.
- W4308590804 created "2022-11-12" @default.
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- W4308590804 date "2022-11-30" @default.
- W4308590804 modified "2023-10-18" @default.
- W4308590804 title "α‐Synuclein as a Target for Metallo‐Anti‐Neurodegenerative Agents" @default.
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- W4308590804 doi "https://doi.org/10.1002/ange.202215360" @default.
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