Skip to main content
Search
Main content
Nature neuroscience
Published

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

Authors

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

Abstract

Nat Neurosci. 2026 Oct 7. doi: 10.1038/s41593-026-02464-0. Online ahead of print.

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.

PMID:42844425 | DOI:10.1038/s41593-026-02464-0

UK DRI Authors

Dr Owen Dando

Senior Bioinformatician

Application of computational techniques, particularly relating to high-throughput sequencing, to neurodegeneration.

Dr Owen Dando

Prof Giampietro Schiavo

Group Leader & Research Division Lead

Restoring axonal transport deficits as a therapeutic strategy for neurodegenerative diseases

Prof Giampietro Schiavo

Prof Siddharthan Chandran

Director & CEO

Dissecting a genetic cause of ALS and FTD and identifying ways to help protect neurons

Prof Siddharthan Chandran