RNA binding proteins and the pathological cascade in ALS/FTD neurodegeneration

Mutant proteins associated with the neurodegenerative diseases ALS and FTD contribute to dysfunction of the intracellular RNA and protein quality control machineries, providing potential targets for developing new therapeutics. Advanced genetic approaches have accelerated the identification of causative genes linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the disease-related proteins encoded by these genes form aggregates in the cellular machineries that regulate RNA and protein quality control in cells. Cross-talk among the signaling pathways governing these machineries leads to pathological cascades mediated by the accumulation of mutant RNA binding proteins. We outline the molecular basis of ALS and FTD pathogenesis and discuss the prospects for therapeutic strategies to treat these diseases.

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