Publications by authors named "Virginia Estades Ayuso"
Background: Perry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin (DCTN1). PS brains accumulate inclusions positive for ubiquitin, transactive-response DNA-binding protein of 43 kDa (TDP-43), and to a lesser extent dynactin.
Objectives: Little is known regarding the contributions of TDP-43, an RNA binding protein that represses cryptic exon inclusion, in PS.
Article Synopsis
- Genetic variation in the TMEM106B gene is linked to the risk and progression of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), with a specific genotype (rs3173615) associated with longer survival after symptoms begin.
- Research shows that the protective genotype is linked to lower accumulation of TMEM106B filaments, while the risk allele correlates with increased TMEM106B core deposition and enhanced TDP-43 dysfunction.
- The findings indicate that managing the accumulation of TMEM106B filaments may be a crucial factor in reducing disease risk and slowing down the progression of FTLD-TDP.
Article Synopsis
- * Researchers analyzed 192 post-mortem brains to identify the accumulation of cryptic RNAs associated with TDP-43 dysfunction, finding significant presence in the amygdala and hippocampus of AD-TDP cases.
- * The findings propose that these cryptic RNAs could serve as valuable diagnostic and therapeutic targets for AD, indicating a potential shared molecular mechanism between AD-TDP and other neurodegenerative conditions like frontotemporal lobar degeneration (FTLD-TDP).
A major function of TAR DNA-binding protein-43 (TDP-43) is to repress the inclusion of cryptic exons during RNA splicing. One of these cryptic exons is in UNC13A, a genetic risk factor for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of cryptic UNC13A in disease is heightened by the presence of a risk haplotype located within the cryptic exon itself.
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