The role of SARM1 in inflammatory and viral neuropathies

SARM1 在炎症和病毒性神经病中的作用

• 批准号: 2251244
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2251244
• 关键词: role; SARM1; inflammatory; viral; neuropathies

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.

科尔曼实验室主要研究损伤性轴突变性，即沃勒氏变性。该实验室在阐明调节沃勒氏变性的分子机制方面发挥了核心作用，并证明该途径在几种疾病模型中被激活，包括青光眼和帕金森病。目前，实验室的工作正试图充分了解NMNAT2和SARM1这两个通路的关键调节因子的作用。SARM1是一种toll样受体衔接蛋白，除了在沃勒氏变性中起作用外，还影响并受许多病毒疾病的影响。作为我硕士项目的延续，我感兴趣的是通过测试病毒感染模型和其他炎症刺激如何影响CNS和pns神经元原代培养中的SARM1水平，来研究SARM1在病毒性和炎症性神经病变中的作用。除了SARM1的表达外，我对是否有病毒和炎症刺激改变SARM1的激活感兴趣。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损失。我还将参与研究，了解SARM1是如何被调节的。这项工作可能最终导致病毒性和炎症性神经病的新治疗方法。

项目成果

SARM1 is a multi-functional NAD(P)ase with prominent base exchange activity, all regulated bymultiple physiologically relevant NAD metabolites.

• DOI: 10.1016/j.isci.2022.103812
• 发表时间: 2022-02-18
• 期刊: iScience
• 影响因子: 5.8
• 作者: Angeletti C;Amici A;Gilley J;Loreto A;Trapanotto AG;Antoniou C;Merlini E;Coleman MP;Orsomando G
• 通讯作者: Orsomando G