SARM1 的出现为 Wallerian 型疾病的治疗提供了新靶点。
Emergence of SARM1 as a Potential Therapeutic Target for Wallerian-type Diseases.
机构信息
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, LRB 826, 364 Plantation Street, Worcester, MA 01605, USA; Program in Chemical Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, LRB 826, 364 Plantation Street, Worcester, MA 01605, USA; Program in Chemical Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
出版信息
Cell Chem Biol. 2020 Jan 16;27(1):1-13. doi: 10.1016/j.chembiol.2019.11.002. Epub 2019 Nov 21.
Wallerian degeneration is a neuronal death pathway that is triggered in response to injury or disease. Death was thought to occur passively until the discovery of a mouse strain, i.e., Wallerian degeneration slow (WLD), which was resistant to degeneration. Given that the WLD mouse encodes a gain-of-function fusion protein, its relevance to human disease was limited. The later discovery that SARM1 (sterile alpha and toll/interleukin receptor [TIR] motif-containing protein 1) promotes Wallerian degeneration suggested the existence of a pathway that might be targeted therapeutically. More recently, SARM1 was found to execute degeneration by hydrolyzing NAD. Notably, SARM1 knockdown or knockout prevents neuron degeneration in response to a range of insults that lead to peripheral neuropathy, traumatic brain injury, and neurodegenerative disease. Here, we discuss the role of SARM1 in Wallerian degeneration and the opportunities to target this enzyme therapeutically.
华勒氏变性是一种神经元死亡途径，是对损伤或疾病的反应而引发的。在发现一种对变性具有抗性的小鼠品系，即华勒氏变性缓慢（WLD）之前，人们认为死亡是被动发生的。鉴于 WLD 小鼠编码一种具有功能获得性融合蛋白，其与人类疾病的相关性有限。后来发现 SARM1（无菌α和 Toll/白细胞介素受体 [TIR] 结构域包含蛋白 1）促进华勒氏变性，表明存在可能具有治疗靶向性的途径。最近，发现 SARM1 通过水解 NAD 来执行变性。值得注意的是，SARM1 的敲低或敲除可防止神经元在一系列导致周围神经病、创伤性脑损伤和神经退行性疾病的损伤下发生变性。在这里，我们讨论 SARM1 在华勒氏变性中的作用以及将这种酶作为治疗靶点的机会。
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