Treatment of Down syndrome: the target was found, it remains to get into it
The method of treatment of Down syndrome is proposed for the first time
Copper news by Sanford-Burnham Medical Research Institute: Unraveling the molecular roots of Down syndromeSpecialists from the Sanford-Burnham Institute of Medical Research (California) have for the first time identified the molecular mechanism behind cognitive impairment in Down syndrome, which allowed them to propose a method for its restoration.
The work was published on March 24 in the journal Nature Medicine (Wang et al., Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome).
During experiments on mice, the authors drew attention to the fact that animals with a "switched off" copy of the SNX27 gene encoding the protein of the same name, and, accordingly, a deficiency of this protein in brain neurons, had symptoms characteristic of Down syndrome, including impaired synaptic connections, decreased learning and memory. Additional studies have shown that people born with this pathology also have reduced levels of the SNX27 protein in nerve cells.
It was found that the protein SNX27 (Sorting nexin family member 27), involved in the regulation of cellular endocytosis, is also responsible for maintaining the required number of glutamate receptors on the surface of neurons – a key link of synaptic connections. Therefore, the deficiency of this protein reduces the number of active glutamate receptors. The new role of SNX27 in the processes occurring in the brain was revealed for the first time.
Trying to understand the relationship between trisomy on chromosome 21 and SNX27 deficiency in Down syndrome, the authors found out that the detected effect is explained by the overexpression of micro-RNA called miR-155, which is encoded by just chromosome 21. It was found that miR-155 suppresses the expression of the SNX27 gene and its excess due to the presence of an additional chromosome causes a lack of SNX27 protein in neurons, a deficiency of active glutamate receptors on their surface, and, as a consequence, synaptic dysfunction, which means impaired learning, memory and behavior.
An image showing the difference between the brain neurons of normal mice (left)
and those who have a deficiency of the SNX27 protein. Illustration by the authors.
The identified mechanism allowed the authors to assume that the compensation of SNX27 deficiency can help restore impaired cognitive function. The experiment on mice was successful – the human protein SNX27 was introduced by gene therapy, after which an increase in the number of glutamate receptors and normalization of brain functions were observed. However, the application of such a technique to humans is still far away, so now the authors are busy searching for molecules that can stimulate the production of SNX27 in the body of patients with Down syndrome.
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