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2016 ; 13
(11
): 1089-1102
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Role of FET proteins in neurodegenerative disorders
#MMPMID27415968
Svetoni F
; Frisone P
; Paronetto MP
RNA Biol
2016[Nov]; 13
(11
): 1089-1102
PMID27415968
show ga
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.
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