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

Astrocytes with C9ORF72 mutation disrupt mitochondrial transport in motor neuron axons, but boosting astrocytic bioenergetics rescues this deficit.

• Why it matters: Understanding how astrocyte dysfunction contributes to ALS is crucial because disrupted axonal transport and mitochondrial impairment are key features of the disease. Addressing this gap could reveal new therapeutic targets for ALS.
• What they did: Researchers used human-induced pluripotent stem-cell-derived astrocytes with the C9ORF72 mutation and cocultured them with motor neurons, then tested gene correction and bioenergetic enhancement strategies to assess effects on mitochondrial transport.
• The result: C9ORF72 mutant astrocytes impair mitochondrial transport in motor neurons, but correcting the mutation or boosting astrocytic mitochondrial function restores transport, highlighting astrocytes' non-cell-autonomous role in ALS.