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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Fig. 1: PUFAs in C9-ALS/FTD.
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Acknowledgements
We thank L. Goodman for critical suggestions.
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Authors and Affiliations
Department of Neurology, Baylor College of Medicine, Houston, TX, USA
Sandeep Kumar Dubey
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Hugo J. Bellen
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USA
Hugo J. Bellen
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA
Hugo J. Bellen
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Sandeep Kumar Dubey
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Dubey, S.K., Bellen, H.J. A neuroprotective role of polyunsaturated fatty acids in C9orf72-ALS/FTD. Nat Neurosci (2025). https://doi.org/10.1038/s41593-025-01920-7
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Published:26 March 2025
DOI:https://doi.org/10.1038/s41593-025-01920-7
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