Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy.

Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy.
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DOI:
10.1111/jns.12219
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发表时间:
2017-09
期刊:
Journal of the peripheral nervous system : JPNS
影响因子:
--
通讯作者:
Höke A
Höke A
中科院分区:
其他
文献类型:
--
作者:
Turkiew E;Falconer D;Reed N;Höke A

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许多周围神经病中出现的远端轴突变性可能与沃勒变性具有共同的分子机制。尽管对周围神经病变小鼠模型的多项研究表明,可以预防慢沃勒变性 (Wlds) 小鼠的轴突变性,但最近发现的沃勒变性参与者 Sarm1 的作用尚未得到广泛探索。在这项研究中,我们发现缺乏 Sarm1 基因的小鼠在紫杉醇引起的化疗引起的周围神经病变模型和高脂肪饮食引起的推定代谢神经病变模型中对远端轴突变性具有抵抗力。这项研究将 Sarm1 的作用扩展到周围神经病中所见的轴突变性,并将其确定为治疗开发的可能目标。
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.
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