Synaptic protein dysregulation in myotonic dystrophy type 1: Disease neuropathogenesis beyond missplicing.

Content Provider	Europe PMC
Author	Hernández-Hernández, Oscar Sicot, Géraldine Dinca, Diana M. Huguet, Aline Nicole, Annie Buée, Luc Munnich, Arnold Sergeant, Nicolas Gourdon, Geneviève Gomes-Pereira, Mário
Copyright Year	2013
Abstract	The toxicity of expanded transcripts in myotonic dystrophy type 1 (DM1) is mainly mediated by the disruption of alternative splicing. However, the detailed disease mechanisms in the central nervous system (CNS) have not been fully elucidated. In our recent study, we demonstrated that the accumulation of mutant transcripts in the CNS of a mouse model of DM1 disturbs splicing in a region-specific manner. We now discuss that the spatial- and temporal-regulated expression of splicing factors may contribute to the region-specific spliceopathy in DM1 brains. In the search for disease mechanisms operating in the CNS, we found that the expression of expanded CUG-containing RNA affects the expression and phosphorylation of synaptic vesicle proteins, possibly contributing to DM1 neurological phenotypes. Although mediated by splicing regulators with a described role in DM1, the misregulation of synaptic proteins was not associated with missplicing of their coding transcripts, supporting the view that DM1 mechanisms in the CNS have also far-reaching implications beyond the disruption of a splicing program.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3927487&blobtype=pdf
Volume Number	1
DOI	10.4161/rdis.25553
PubMed Central reference number	PMC3927487
PubMed reference number	25003003
Journal	Rare Diseases [Rare Dis]
e-ISSN	21675511
Language	English
Publisher	Landes Bioscience
Publisher Date	2013-06-26
Access Restriction	Open
Rights License	This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. Copyright © 2013 Landes Bioscience
Subject Keyword	myotonic dystrophy type 1 trinucleotide repeat expansion RNA toxicity RNA splicing central nervous system transgenic mice synaptic function synaptic protein RAB3A synapsin I
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine