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• W2956075921 abstract "Recent genetic and biochemical evidence has improved our understanding of the pathomechanisms that lead to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurodegenerative diseases with overlapping symptoms and causes. Impaired RNA metabolism, enhanced aggregation of protein-RNA complexes, aberrant formation of ribonucleoprotein (RNP) granules and dysfunctional protein clearance via autophagy are emerging as crucial events in ALS/FTD pathogenesis. Importantly, these processes interact at the molecular level, converging on a common pathogenic cascade. In this review, we summarize key principles underlying ALS and FTD, and we discuss how mutations in genes involved in RNA metabolism, protein quality control and protein degradation meet mechanistically to impair the functionality and dynamics of RNP granules, and how this leads to cellular toxicity and death. Finally, we describe recent advances in understanding signaling pathways that become dysfunctional in ALS/FTD, partly due to altered RNP granule dynamics, but also with stress granule-independent mechanisms and, thus could be promising targets for future therapeutic intervention." @default.
• W2956075921 created "2019-07-12" @default.
• W2956075921 creator A5008277442 @default.
• W2956075921 creator A5015180743 @default.
• W2956075921 creator A5035021417 @default.
• W2956075921 creator A5053912816 @default.
• W2956075921 date "2020-03-01" @default.
• W2956075921 modified "2023-10-10" @default.
• W2956075921 title "ALS and FTD: Where RNA metabolism meets protein quality control" @default.
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