کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6264292 | 1613977 | 2012 | 13 صفحه PDF | دانلود رایگان |

Amyotrophic lateral sclerosis (ALS) research is undergoing an era of unprecedented discoveries with the identification of new genes as major genetic causes of this disease. These discoveries reinforce the genetic, clinical and pathological overlap between ALS and frontotemporal lobar degeneration (FTLD). Common causes of these diseases include mutations in the RNA/DNA-binding proteins, TDP-43 and FUS/TLS and most recently, hexanucleotide expansions in the C9orf72 gene, discoveries that highlight the overlapping pathogenic mechanisms that trigger ALS and FTLD. TDP-43 and FUS/TLS, both of which participate in several steps of RNA processing, are abnormally aggregated and mislocalized in ALS and FTLD, while the expansion in the C9orf72 pre-mRNA strongly suggests sequestration of one or more RNA binding proteins in pathologic RNA foci. Hence, ALS and FTLD converge in pathogenic pathways disrupting the regulation of RNA processing.This article is part of a Special Issue entitled RNA-Binding Proteins.
⺠Amyotrophic lateral sclerosis and Frontotemporal lobar degeneration have clinical, genetic and pathological overlap. ⺠ALS and FTLD converge in pathogenic pathways disrupting the regulation of RNA processing. ⺠Identification of TDP-43 RNA targets highlights its multifunctional role in RNA processing. ⺠TDP-43 autoregulation provides a model for a feed-forward mechanism driving disease progression in TDP-43 proteinopathies.
Journal: Brain Research - Volume 1462, 26 June 2012, Pages 3-15