Sarm1 基因缺失对两种周围神经病模型具有神经保护作用。
Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy.
机构信息
Department of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
出版信息
J Peripher Nerv Syst. 2017 Sep;22(3):162-171. doi: 10.1111/jns.12219.
Abstract
Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development.
摘要
在许多周围神经病中观察到的远端轴突变性可能与 Wallerian 变性具有共同的分子机制。虽然几种周围神经病的小鼠模型研究表明，在缓慢的 Wallerian 变性（Wlds）小鼠中可以预防轴突变性，但最近在 Wallerian 变性中发现的一个参与者 Sarm1 的作用尚未得到广泛探索。在这项研究中，我们表明，缺乏 Sarm1 基因的小鼠对紫杉醇引起的化疗诱导的周围神经病模型和高脂肪饮食诱导的假定代谢性神经病模型中的远端轴突变性具有抗性。这项研究将 Sarm1 的作用扩展到周围神经病中观察到的轴突变性，并将其确定为治疗开发的可能靶标。
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本文引用的文献
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Brain. 2016 Dec;139(Pt 12):3092-3108. doi: 10.1093/brain/aww251. Epub 2016 Oct 25.
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