Genetic and molecular bases of Aicardi-Goutières Syndrome (AGS)
DOI:
https://doi.org/10.19230/jonnpr.1616Keywords:
Aicardi-Goutières Syndrome, Interferon-α, RNaseH2, cGAS-STING, Autoimmunity, proinflammatory cytokine, ribonucleotide excision repairAbstract
Objetive: The purpose of this work was to demonstrate the connection between the mutations in any of the RNaseH2 complex’s subunits and the symptoms that showed the patients affected with AGS due to the role that RNaseH2 has in nucleic acid metabolism.
Method: it refers to some experiments that the samples consisted of Saccharomyces cerevisiae yeast cells, lymphoblastoid cell line from an AGS patient and fibroblast cell line from mice with orthologous mutations in the RNaseH2 complex to those found in cells of patients with AGS. They also used techniques such as measurement of loss of heterozygosity (LOH), PCR, RNA isolation and a successive RT-PCR, siRNA and CRISP / cas9 as well as Mann-Whitney statistical analysis and median method.
Results: From these experiments it can be corroborated that due to a decrease in the specific activity of ribonucleotide excision repair, there is an accumulation of inusual species of nucleic acids that results in an autoimmune response possibly triggered by the cGASSTING pathway with the consequent release of INF-?.
Conclusions: The release of INF-? is probably the cause of the symptoms associated with this syndrome, both in vascular and neurological damage, although there is some uncertainty in this statement, because other factors could also be involved.
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