title: Role of FET proteins in neurodegenerative disorders.
abstract: Neurodegenerative disorders such as Alzheimer disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) affect different neuronal cells, and have a variable age of onset, clinical symptoms, and pathological features. Despite the great progress in understanding the etiology of these disorders, the underlying mechanisms remain largely unclear. Among the processes affected in neurodegenerative diseases, alteration in RNA metabolism is emerging as a crucial player. RNA-binding proteins (RBPs) are involved at all stages of RNA metabolism and display a broad range of functions, including modulation of mRNA transcription, splicing, editing, export, stability, translation and localization and miRNA biogenesis, thus enormously impacting regulation of gene expression. On the other hand, aberrant regulation of RBP expression or activity can contribute to disease onset and progression. Recent reports identified mutations causative of neurological disorders in the genes encoding a family of RBPs named FET (FUS/TLS, EWS and TAF15). This review summarizes recent works documenting the involvement of FET proteins in the pathology of ALS, FTLD, essential tremor (ET) and other neurodegenerative diseases. Moreover, clinical implications of recent advances in FET research are critically discussed.
authors.affiliation: a University of Rome "Foro Italico," , Rome , Italy.|b Laboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia , Rome , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Svetoni
authors.affiliation: b Laboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia , Rome , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Frisone
authors.affiliation: a University of Rome "Foro Italico," , Rome , Italy.|b Laboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia , Rome , Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Paronetto
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; C000599550:FUS protein, human; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors; D012313:RNA
keywords: ALS; EWS; FUS; TAF15; neurodegenerative disorders