神经退行性变
神经保护
神经科学
星形胶质细胞
小胶质细胞
神经毒性
神经营养因子
生物
疾病
医学
受体
中枢神经系统
炎症
免疫学
内科学
毒性
作者
Jared T. Hinkle,Valina L. Dawson,Ted M. Dawson
摘要
Abstract We recently demonstrated that NLY01, a novel glucagon‐like peptide‐1 receptor agonist, exerts neuroprotective effects in two mouse models of PD in a glia‐dependent manner. NLY01 prevented microglia from releasing inflammatory mediators known to convert astrocytes into a neurotoxic A1 reactive subtype. Importantly, we provided evidence that this neuroprotection was not mediated by a direct action of NLY01 on neurons or astrocytes (e.g., by activating neurotrophic pathways or modulating astrocyte reactivity per se). In the present article, we provide a generalist review of microglia and astrocytes in neurodegeneration and discuss the emerging paradigm of A1 astrocyte neurotoxicity in more detail. We comment on specific inferences that are naturally suggested by our work in this area and the differential level of support it offers to each. Finally, we discuss implications for the overall goal of creating disease‐modifying therapies for PD, survey emerging methodologies for accelerating translational research on glia in neurodegeneration, and describe expected challenges for developing glia‐directed therapies that do not impede essential physiological functions carried out by glia in the CNS. © 2019 International Parkinson and Movement Disorder Society
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