NLRP1炎性体是神经元轴突修剪的一个重要和选择性介质。

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-02-26 DOI:10.1038/s44319-025-00402-y

Selena E Romero, Matthew J Geden, Richa Basundra, Kiran Kelly-Rajan, Edward A Miao, Mohanish Deshmukh

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引用次数: 0

摘要

轴突修剪是神经元在保持神经元细胞体完整的情况下选择性地使轴突分支退化的独特过程。轴突修剪的机制与细胞凋亡的机制有许多共同之处。轴突修剪和凋亡通路都需要关键的凋亡蛋白（Bax, Caspase-9, Caspase-3）。有趣的是，轴突修剪不需要Apaf-1， Apaf-1是凋亡复合物的关键成员。因此，在轴突修剪过程中，半胱天冬酶是如何以凋亡无关的方式被激活的尚不清楚。在这里，我们发现神经元利用NLRP1炎性小体，病原体的先天免疫传感器，专门用于轴突修剪。引人注目的是，nlrp1b缺陷神经元在体外和体内都不能修剪轴突，但在细胞凋亡过程中完全能够退化。我们的研究结果表明NLRP1是一种免疫分子，它与神经元有关，具有意想不到的生理功能，独立于病原体诱导的促炎作用。

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The NLRP1 inflammasome is an essential and selective mediator of axon pruning in neurons.

Axon pruning is a unique process neurons utilize to selectively degenerate axon branches while keeping the neuronal cell body intact. The mechanisms of axon pruning have much in common with those of apoptosis. Both axon pruning and apoptosis pathways require key apoptotic proteins (Bax, Caspase-9, Caspase-3). Interestingly, axon pruning does not require Apaf-1, a key member of the apoptosome complex. As such, exactly how caspases are activated in an apoptosome-independent manner during axon pruning is unknown. Here we show that neurons utilize the NLRP1 inflammasome, an innate immune sensor of pathogens, specifically for axon pruning. Strikingly, NLRP1b-deficient neurons were unable to prune axons both in vitro and in vivo, but fully capable of degenerating during apoptosis. Our results reveal NLRP1 as an immune molecule engaged by neurons for an unexpected physiological function independent of its pathogen-induced proinflammatory role.

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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