Axon degeneration is a prominent feature of the injured nervous system, occurs across neurological diseases, and drives functional loss in neural circuits. We have seen a paradigm shift in the last decade with the realization that injured axons are capable of actively driving their own destruction through the sterile-alpha and TIR motif containing 1 (SARM1) protein. Early studies of Wallerian degeneration highlighted a central role for NAD+ metabolites in axon survival, and this association has grown even stronger in recent years with a deeper understanding of SARM1 biology. Here, we review our current knowledge of SARM1 function in vivo and our evolving understanding of its complex architecture and regulation by injury-dependent changes in the local metabolic environment. The field is converging on a model whereby SARM1 acts as a sensor for metabolic changes that occur after injury and then drives catastrophic NAD+ loss to promote degeneration. However, a number of observations suggest that SARM1 biology is more complicated, and there remains much to learn about how SARM1 governs nervous system responses to injury or disease.

中文翻译：

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受损神经系统中的 SARM1 信号传导机制。

轴突变性是受损神经系统的一个突出特征，发生在神经系统疾病中，并导致神经回路的功能丧失。我们已经看到在过去十年中发生了范式转变，意识到受伤的轴突能够通过含有 1 (SARM1) 蛋白的无菌-α 和 TIR 基序主动驱动它们自己的破坏。Wallerian 变性的早期研究强调了 NAD+ 代谢物在轴突存活中的核心作用，近年来，随着对 SARM1 生物学的深入了解，这种关联变得更加强大。在这里，我们回顾了我们目前对 SARM1 体内功能的了解，以及我们对其复杂结构和通过局部代谢环境中损伤依赖性变化调节的不断发展的理解。该领域正在融合一个模型，在该模型中，SARM1 充当损伤后发生的代谢变化的传感器，然后驱动灾难性的 NAD+ 损失以促进退化。然而，许多观察表明 SARM1 生物学更为复杂，关于 SARM1 如何控制神经系统对损伤或疾病的反应还有很多需要了解。