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 two to five years of diagnosis. Much of the current research centers on understanding why proteins such as TDP-43 and FUS/TLS—normally involved in regulating how RNA is processed in the cell nucleus—misfold and accumulate into toxic aggregates in the cytoplasm, and how mutations in the C9ORF72 gene produce repetitive RNA sequences that appear to poison neurons through multiple converging mechanisms. A central open question is whether the damage arises primarily from the loss of these proteins' normal functions, from the direct toxicity of the aggregates they form, or from both simultaneously—a distinction that matters enormously for designing therapies. Researchers are also investigating the overlap between ALS and frontotemporal dementia, conditions that share genetic causes and pathological features including ubiquitin-positive inclusions, and exploring whether factors like progranulin deficiency connect neuroinflammation to neuronal death in ways that might be therapeutically targeted.

Works

62,362

Total citations

1,457,437

Keywords

TDP-43FUS/TLSC9ORF72mutationsneurodegenerationmotor neurons