Stress-dependent modification of a protein called TDP-43 helps neurons recover once the stress has passed
Many neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), are linked to improper function of a protein called TDP-43. Under healthy conditions, TDP-43 is found inside the nucleus of neurons, where it plays critical roles in maintaining neuronal health. In disease however, TDP-43 leaves the nucleus and forms toxic aggregates, a key pathological feature of both ALS and FTD. Aging and other cellular stresses are thought to contribute to this process, but the mechanisms that protect TDP-43 have remained unclear.
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Suk, T.R., Part, C.E., Nguyen, T.T., Zhang, J.L., Heer, M.M., Caballero-Gómez, A., Grybas, V.S., McKeever, P.M., Nguyen, B., Ali, T., Callaghan, S.M., Woulfe, J.M., Robertson, J., and Rousseaux, M.W.C. A stress-dependent TDP-43 SUMOylation program preserves neuronal function. (2025) – Molecular Neurodegeneration 20 (38). DOI:
