The role of SARM1 in inflammatory and viral neuropathies

科尔曼实验室主要专注于损伤诱导的轴突变性，即沃勒变性。实验室在阐明沃勒变性的分子机制方面发挥了核心作用，并已证明该途径在几种疾病模型中都被激活，包括青光眼和帕金森病。目前，该实验室的工作人员正在试图完全了解该途径的两个关键调节因子NMNA2和Sarm1的作用。Sarm1是一种Toll样受体适配器蛋白，除了在沃勒变性中发挥作用外，还影响许多病毒疾病。作为我MPhil项目的继续，我有兴趣通过测试原代培养的CNS和PNS神经元中的Sarm1水平如何受到病毒感染模型和其他炎症刺激的影响，来研究Sarm1在病毒和炎症性神经疾病中的作用。除了Sarm1的表达，IAI还感兴趣的是测试是否有任何病毒和炎症刺激改变Sarm1的激活。我的总体目标是研究Sarm1表达和/或激活的变化是否会导致轴突和细胞体的丧失。我还将参与研究，以了解Sarm1是如何受到监管的。这项工作可能最终导致新的治疗病毒性和炎症性神经病的方法。

The Coleman laboratory has primarily focused on injury-induced axon degeneration, known as Wallerian degeneration.The lab has played a central role in elucidating the molecular mechanisms regulating Wallerian degeneration and hasdemonstrated that the pathway is activated in several disease models, including glaucoma and Parkinson's disease.Work in the lab is currently trying to fully understand the roles of NMNAT2 and SARM1, the two key regulators of thepathway. SARM1 is a Toll-like receptor adaptor protein, which in addition to its role in Wallerian degeneration, influencesand is influenced by a number of viral disorders. As a continuation of my MPhil project, I am interested in investigatingthe role of SARM1 in viral and inflammatory neuropathies by testing how SARM1 levels in primary cultures of CNS andPNS neurons are affected by models of viral infection and other inflammatory stimuli. As well as SARM1 expression, Iam interested in testing whether any viral and inflammatory stimuli alter SARM1 activation. My overall aim is toinvestigate whether changes in SARM1 expression and/or activation lead to axon and cell body loss. I will also contributeto studies to understand how SARM1 is regulated. This work may ultimately lead to new treatments for viral andinflammatory neuropathies.