![]() TDP-43 is an RNA processing protein and is known to be intricately involved in RNA metabolism 5, 6, 7. One of the main pathogenic features of ALS are cytoplasmic aggregates of an otherwise predominantly nuclear DNA- and RNA-binding protein TDP-43 (TAR DNA-binding protein) in affected neurons, however, mutations of this protein in patients are too rare to explain this phenomenon 2, 3, 4. What is becoming increasingly clear, however, is that a complex molecular interplay contributes to this disorder, of which many components are closely involved in RNA metabolism. ![]() Whether the denervation is initiated primarily in the CNS or by the muscle itself remains under debate 1. Furthermore, the identified miRNAs are predicted to target proteins that are involved in both normal processes and various muscle disorders and indicate muscle tissue is undergoing active reinnervation/compensatory attempts thus providing targets for further research and therapy development in ALS.Īmyotrophic lateral sclerosis (ALS) is a late-onset disorder primarily affecting upper and lower motor neurons leading to progressive and severe skeletal muscle atrophy. The identified snoRNAs, mtRNAs and other small RNAs provide possible molecular links between insulin signaling and ALS. Following small RNA-Seq, we compared the expression of small RNAs in muscle tissue of ALS patients and healthy age-matched controls. Several myomiRs have shown promise for therapeutic use in cellular and animal models of ALS however, the exact miRNA species differentially expressed in muscle tissue of ALS patients remain unknown. In muscle, miRNAs called myomiRs govern important processes and are deregulated in various disorders. Small RNAs, including microRNAs (miRNAs), can serve as important regulators of gene expression and can act both globally and in a tissue-/cell-type-specific manner. Amyotrophic lateral sclerosis is a late-onset disorder primarily affecting motor neurons and leading to progressive and lethal skeletal muscle atrophy.
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