C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis

摘要: C9orf72 hexanucleotide repeat expansions are the most common cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. The clinical presentation is often indistinguishable from classic FTD or ALS, although neuropsychiatric symptoms more prevalent and, for behavioural cognitive occur frequently. Pathogenic length in hundreds thousands, but minimum that increases risk disease, how whether size affects phenotype, unclear. Like many patients with neuronal inclusions contain TARDBP seen, not universal, characteristic pathological finding dipeptide (DPR) proteins, formed by unconventional repeat-associated non-ATG translation. Possible mechanisms neurodegeneration include loss protein function, RNA toxicity, toxicity DPR which these major pathogenic mechanism yet certain.