New research shows that lipid metabolism genes are downregulated in patient samples and Drosophila models of amyotrophic lateral sclerosis or frontotemporal dementia associated with expansions in C9orf72, resulting in reduced levels of phospholipids containing polyunsaturated fatty acids. Importantly, increasing polyunsaturated fatty acids through diet or genetic modulation of C9orf72 in Drosophila or induced pluripotent stem cell-derived motor neurons significantly improves neuronal survival.
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We thank L. Goodman for critical suggestions.
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Dubey, S.K., Bellen, H.J. A neuroprotective role of polyunsaturated fatty acids in C9orf72-ALS/FTD. Nat Neurosci 28, 710–712 (2025). https://doi.org/10.1038/s41593-025-01920-7
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DOI: https://doi.org/10.1038/s41593-025-01920-7
