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Interaction of RAGE with α-synuclein fibrils mediates inflammatory response of microglia

Cell Rep. 2022-09; 
Houfang Long, Shengnan Zhang, Shuyi Zeng, Yilun Tong, Jun Liu, Cong Liu, Dan Li
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Proteins, Expression, Isolation and Analysis … The sample solutions were boiled for 15 min and loaded on a 4–20% SurePAGE gel (GenScript, M00655) and then transferred to 0.2 μm PVDF membranes (Millipore, ISEQ10100). The … Get A Quote

摘要

Microglia-mediated neuroinflammation and α-synuclein (α-syn) aggregation, both as pathological hallmarks of Parkinson's disease (PD), crosstalk to exacerbate degeneration of dopaminergic neurons and PD progression. However, the mechanism underlying their interaction is poorly understood, which obstructs effective therapeutic inhibition of α-syn-induced neuroinflammation. Here, we initiate from structure-based interaction predictions and find that receptor for advanced glycation end products (RAGE) serves as a receptor of α-syn fibrils on microglia. Results of nuclear magnetic resonance (NMR) spectroscopy and mutagenesis validate that the V domain of RAGE that contains an alkaline surface can bind with acidi... More

关键词

CP: Neuroscience, Parkinson's disease, RAGE, microglia, neuroinflammation, α-synuclein