Cytotoxic Impact of Tau Oligomers and RNA-Binding Proteins (RBPs) in Neurodegenerative Diseases.

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Background

RNA-binding proteins (RBPs) facilitate ribonucleoprotein complex (RNP) formation to coordinate RNA processing and post-transcriptional gene regulation. All RNA molecules are bound by specific sets of RBPs that regulate correct processing, transport, stability, and final degradation. RBPs play roles in several RNA processing steps including transcription (TAF15, EWS, FUS), alternative splicing (TDP-43, FUS, TAF15, hnRNPA1, hnRNPA2/B1, EWS), alternative polyadenylation, transcript localization, sequestration into inclusions and stress granules, translation, RNA degradation, and turnover (MATR3). RBPs and impaired RNA processing have been implicated in the onset and progression of several neurodegenerative diseases. Many cellular mechanisms are altered in neurodegenerative diseases, including the mislocalization of RBPs. RBPs interact with tau to alter the physiology of stress granules and they aggregate in tauopathies. Some notable RBPs such as Transactive Response DNA Binding Protein (TDP-43), Fused in Sarcoma (FUS), T-cell Intracytoplasmic Antigen (TIA-1) and many other are dysregulated in neurodegenerative diseases.

We propose an exciting opportunity to show in this Research Topic up and coming and recent evidences on early impact of tau toxic species and RBPs in neurons. In the last ten years many researchers focus attention on how misfolded and aggregating proteins (amyloid-beta, tau and a-Synuclein) determine the pathogenesis of diseases like Alzheimer's and Parkinson Diseases. Recently new findings are supporting a close and interesting cross-talk between Tau and RNA-Binding Proteins (RBPs) in the pathogenesis and progression of several neuronal diseases. In this context the goal of this research topic is collect and publish all the most recent findings that elucidate this toxic cellular and molecular cross-talk.

The scope is collect original manuscript that describe cytotoxic effects of Tau (species) in in-vitro and in-vivo models in RNA metabolism processes and context. Particularly, research on toxic relationship between Tau and RNA-Binding Proteins will be evaluated. RNA metabolism includes: Protein Synthesis/Ribosomes, Splicing, mRNA Poly-Adenilation, mRNA degradation, Ribonucleoprotein complexes, RNA-Binding Proteins regulations. The scope includes also attention on organelle-specific toxic effects of these interactions including synaptic dysfunction and organelle-specific impact like mitochondrial, lysosomal and nuclear dysfunctions.

Keywords: Tau, Oligomers, RNA-Binding Proteins, Organelles, Neurodegeneration

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