Astrocytes regulate axonal mitochondrial transport deficits in C9ORF72 amyotrophic lateral sclerosis motor neurons

IF 20.3 1区医学 Q1 NEUROSCIENCES

Nature neuroscience Pub Date : 2026-10-07 DOI:10.1038/s41593-026-02464-0

Maria Stavrou,Áine Bríd Heffernan,Roderick N. Carter,Owen Dando,Zoeb Jiwaji,Karen Burr,Jyoti Nanda,David Villarroel-Campos,Alya Masoud Abdelhafid,Justyna Cholewa-Waclaw,Daniel Soong,David Story,Giampietro Schiavo,Giles E. Hardingham,Siddharthan Chandran,Bhuvaneish T. Selvaraj

引用次数: 0

Abstract

Abstract Disrupted axonal transport and astrocyte dysfunction are implicated in amyotrophic lateral sclerosis (ALS). Here we show these processes are linked—human-induced pluripotent stem-cell-derived astrocytes carrying the C9ORF72 mutation disrupt mitochondrial axonal transport and mitochondrial function in cocultured motor neurons (MNs). Conversely, isogenic gene-corrected astrocytes or boosting astrocytic mitochondrial bioenergetics rescue axonal mitochondrial transport deficits in C9ORF72 MNs. Our results delineate a non-cell-autonomous role for astrocytes in regulating mitochondrial transport along axons in ALS models.

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星形胶质细胞调节C9ORF72肌萎缩侧索硬化症运动神经元轴突线粒体运输缺陷

轴突运输中断和星形胶质细胞功能障碍与肌萎缩侧索硬化（ALS）有关。在这里，我们发现这些过程是相互关联的——人类诱导的多能干细胞来源的星形胶质细胞携带C9ORF72突变，在共培养的运动神经元（MNs）中破坏线粒体轴突运输和线粒体功能。相反，等基因校正的星形细胞或增强星形细胞线粒体生物能量可以挽救C9ORF72 MNs的轴突线粒体运输缺陷。我们的研究结果描述了在ALS模型中星形胶质细胞在调节线粒体沿轴突运输中的非细胞自主作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature neuroscience 医学-神经科学

CiteScore

38.60

自引率

1.20%

发文量

212

审稿时长

1 months

期刊介绍： Nature Neuroscience, a multidisciplinary journal, publishes papers of the utmost quality and significance across all realms of neuroscience. The editors welcome contributions spanning molecular, cellular, systems, and cognitive neuroscience, along with psychophysics, computational modeling, and nervous system disorders. While no area is off-limits, studies offering fundamental insights into nervous system function receive priority. The journal offers high visibility to both readers and authors, fostering interdisciplinary communication and accessibility to a broad audience. It maintains high standards of copy editing and production, rigorous peer review, rapid publication, and operates independently from academic societies and other vested interests. In addition to primary research, Nature Neuroscience features news and views, reviews, editorials, commentaries, perspectives, book reviews, and correspondence, aiming to serve as the voice of the global neuroscience community.