title: Targeting RNA binding proteins involved in neurodegeneration.
abstract: Dysfunctions at the level of RNA processing have recently been shown to play a fundamental role in the pathogenesis of many neurodegenerative diseases. Several proteins responsible for these dysfunctions (TDP-43, FUS/TLS, and hnRNP A/Bs) belong to the nuclear class of heterogeneous ribonucleoproteins (hnRNPs) that predominantly function as general regulators of both coding and noncoding RNA metabolism. The discovery of the importance of these factors in mediating neuronal death has represented a major paradigmatic shift in our understanding of neurodegenerative processes. As a result, these discoveries have also opened the way toward novel biomolecular screening approaches in our search for therapeutic options. One of the major hurdles in this search is represented by the correct identification of the most promising targets to be prioritized. These may include aberrant aggregation processes, protein-protein interactions, RNA-protein interactions, or specific cellular pathways altered by disease. In this review, we discuss these four major options together with their various advantages and drawbacks.
authors: 1Department of Life Sciences, University of Trieste, Trieste, Italy.
authors: Maurizio
authors: M
authors: Romano
authors: Emanuele
authors: E
authors: Buratti
mesh_terms: D016923:Cell Death / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D005427:Flocculation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D022661:RNA, Untranslated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D012261:Ribonucleoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D012333:RNA, Messenger; D022661:RNA, Untranslated; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; D054852:Small Molecule Libraries
keywords: ALS; FTLD; RNA binding proteins; TDP-43; hnRNP; review