Amyotrophic Lateral Sclerosis Research

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease in which the motor neurons that control voluntary movement progressively die, leading to paralysis and, typically, death within a few years of diagnosis. Research into its molecular basis has converged on a handful of proteins — most notably TDP-43, FUS/TLS, and the product of the C9ORF72 gene — that normally help regulate how RNA is processed inside cells but form toxic aggregates in diseased neurons, often appearing as the ubiquitin-positive inclusions that pathologists observe in post-mortem tissue. Because mutations in these same genes also cause frontotemporal dementia, investigators are working to understand why different mutations in shared molecular machinery produce such distinct clinical pictures in different patients, and whether restoring normal RNA processing or clearing aberrant protein deposits could slow or halt neurodegeneration. The role of progranulin deficiency in modulating disease severity has added another layer of complexity, pointing toward immune and lysosomal pathways as potential therapeutic targets alongside the better-studied genetic drivers.

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61,398

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Keywords

TDP-43FUS/TLSC9ORF72mutationsneurodegenerationmotor neurons