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

Abstract

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 cascadesmediated by the accumulation of mutant RNA binding proteins.We outline themolecular basis of ALS and FTD pathogenesis and discuss the prospects for therapeutic strategies to treat these diseases.