RNA Metabolism in Neurodegenerative Disease

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Abstract:

RNA metabolism is a vital process through which RNA is produced, transported, regulated, stored, and translated or degraded. Recently, the discoveries of mutations in key RNA binding proteins involved in several human neuronal based diseases have firmly placed the process of RNA metabolism as central to disease etiology. This review first recaps the process of RNA metabolism in the mammalian neuron and describes the roles of RNA granules in this process. Using the recently described alterations in TAR DNA binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) in amyotrophic lateral sclerosis (ALS) and frontal temporal lobar degeneration (FTLD), we discuss how RNA binding protein abnormalities can affect RNA metabolism. We then discuss two additional RNA based mechanisms distinct from alterations in RNA binding protein function that impact RNA metabolism and result in disease. Cumulatively, these observations provide strong support for the hypothesis that alterations in RNA metabolism can lead to neurodegenerative disease, including ALS.





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  • Current Chemical Biology aims to publish full-length and mini reviews on exciting new developments at the chemistry-biology interface, covering topics relating to Chemical Synthesis, Science at Chemistry-Biology Interface and Chemical Mechanisms of Biological Systems.

    Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).

    Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs).
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