DOMS, COX-2, GDNF, Glial cells, muscle cells,

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832118/

大鼠运动后的机械痛觉过敏需要通过肌肉中环氧合酶 2 激活上调神经胶质细胞系衍生的神经营养因子

In a healthy adult brain, glial cell line-derived neurotrophic factor (GDNF) is exclusively expressed by neurons, and, in some instances, it has also been shown to derive from a single neuronal subpopulation. Secreted GDNF acts in a paracrine fashion by forming a complex with the GDNF family receptor α1 (GFRα1), which is mainly expressed by neurons and can act in cis as a membrane-bound factor or in trans as a soluble factor. The GDNF/GFRα1 complex signals through interactions with the “rearranged during transfection” (RET) receptor or via the neural cell adhesion molecule (NCAM) with a lower affinity. GDNF can also signal independently from GFRα1 by interacting with syndecan-3. RET, which is expressed by neurons involved in several pathways (nigro–striatal dopaminergic neurons, motor neurons, enteric neurons, sensory neurons, etc.), could be the main determinant of the specificity of GDNF’s pro-survival effect. In an injured brain, de novo expression of GDNF occurs in glial cells. Neuroinflammation has been reported to induce GDNF expression in activated astrocytes and microglia, infiltrating macrophages, nestin-positive reactive astrocytes, and neuron/glia (NG2) positive microglia-like cells. This disease-related GDNF overexpression can be either beneficial or detrimental depending on the localization in the brain and the level and duration of glial cell activation. Some reports also describe the upregulation of RET and GFRα1 in glial cells, suggesting that GDNF could modulate neuroinflammation. Keywords: glial-cell-line-derived neurotrophic factor, microglia, astrocyte, neuroinflammation, rearranged during transfection, GDNF family receptor alpha 1, gene therapy, Parkinson’s disease

在健康的成人大脑中，神经胶质细胞系衍生的神经营养因子 (GDNF) 仅由神经元表达，并且在某些情况下，它也被证明源自单个神经元亚群。分泌的 GDNF 通过与 GDNF 家族受体 α1 (GFRα1) 形成复合物以旁分泌方式发挥作用，GDNF 家族受体 α1 (GFRα1) 主要由神经元表达，可以顺式作为膜结合因子或反式作为可溶性因子。 GDNF/GFRα1 复合物通过与“转染期间重排”(RET) 受体相互作用或通过亲和力较低的神经细胞粘附分子 (NCAM) 发出信号。 GDNF 还可以通过与 syndecan-3 相互作用而独立于 GFRα1 发出信号。 RET 由涉及多个通路的神经元（黑质-纹状体多巴胺能神经元、运动神经元、肠神经元、感觉神经元等）表达，可能是 GDNF 促生存作用特异性的主要决定因素。在受伤的大脑中，GDNF 的从头表达发生在神经胶质细胞中。据报道，神经炎症会在活化的星形胶质细胞和小胶质细胞、浸润性巨噬细胞、巢蛋白阳性反应性星形胶质细胞和神经元/胶质细胞 (NG2) 阳性小胶质细胞样细胞中诱导 GDNF 表达。这种与疾病相关的 GDNF 过表达可能是有益的，也可能是有害的，这取决于大脑中的定位以及神经胶质细胞活化的水平和持续时间。一些报告还描述了神经胶质细胞中 RET 和 GFRα1 的上调，表明 GDNF 可以调节神经炎症。

关键词：神经胶质细胞源性神经营养因子，小胶质细胞，星形胶质细胞，神经炎症，转染过程中重排，GDNF 家族受体 alpha 1，基因治疗，帕金森病