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Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease.

Nat. Med.. 2018; 
YunSeung Pil,KamTae-In,PanickerNikhil,KimSangMin,OhYumin,ParkJong-Sung,KwonSeung-Hwan,ParkYong Joo,KaruppagounderSenthilkumar S,ParkHyejin,KimSangjune,OhNayeon,KimNayoung Alice,LeeSaebom,BrahmachariSaurav,MaoXiaobo,LeeJun Hee,KumarManoj,AnDaniel,KangSung-Ung,LeeYunjong,LeeKang Choon,NaDong Hee,KimDonghoon,LeeSang Hun,RoschkeViktor V,LiddelowShane A,MariZoltan,BarresBen A,DawsonValina L,LeeSeulki,DawsonTed M,KoHan
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Proteins, Expression, Isolation and Analysis Recombinant mouse α-synuclein proteins were purified as previously described with an IPTGindependent inducible pRK172 vector system15,36. Endotoxin was depleted by ToxinEraser endotoxin removal kit (Genscript). GLP1R-transfected HEK293 Cre-Luc-GLP1R cells (GenScript, Piscataway, NJ, USA) were treated with serial dilutions of [Cys40]exendin-4 and NLY01 at the indicated concentrations. Both GLP1R-transfected cells and cAMP detection reagents are part of the intracellular cAMP human recombinant GLP1R stable cell line assay (GenScript). Get A Quote

摘要

Activation of microglia by classical inflammatory mediators can convert astrocytes into a neurotoxic A1 phenotype in a variety of neurological diseases. Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease-modifying therapies. Glucagon-like peptide-1 receptor (GLP1R) agonists have been indicated as potential neuroprotective agents for neurologic disorders such as Alzheimer's disease and Parkinson's disease. The mechanisms by which GLP1R agonists are neuroprotective are not known. Here we show that a potent, brain-penetrant long-acting GLP1R agonist, NLY01, protects against the loss of dopaminergic neurons and ... More

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