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DYRK1A gene may be 1 of most influential factors in Down syndrome
Date:3/1/2010

Research undertaken in recent years on Down's syndrome has focused on the DYRK1A gene. The superexpression of this gene affects transmission in the neurones, according to Mr Garikoitz Azkona. In his PhD thesis, The molecular bases of neuropathology in Down's syndrome: the role of DYRK1A, Mr Azkona argues that this failure in neurone transmission could be behind the problem that persons with Down's syndrome have regarding visual-spatial memory.

Persons with Down's syndrome usually have great problems with memory; this being precisely one of the characteristics which differentiates them from other people. Particularly notable is the poor capacity they have for retaining information received orally, but also that concerning visual-spatial memory should be taken into account. This topic has hardly been dealt with to date and Mr Azkona decided to take up the challenge. Starting with this differential phenomenon, he has little by little unravelled the problem until he came up with the DYRK1A gene.

To begin his research, Mr Azkona evaluated the psychomotricity of persons with Down's syndrome as well as their progress as they got older, using a test known as the tapping test. As was expected, it was proven that, in the short term, persons with Down's syndrome have poorer visual-spatial memory; he also concluded that they take longer in doing the tests than those not having the syndrome and sufferers do not use as effective cognitive strategies as non-sufferers.

It is believed that the root of this problem is in the central part of the brain; more concretely, in the transmission between the hippocampus and a specific part of the brain. It would seem that cholinergic neurones, which should guarantee this transmission, undergo alterations in those persons with Down's syndrome, besides deteriorating with age. The DYRK1A gene is thought to have much to do with this and Mr Azkona based his hypothesis on this for his research work.

Communication between cholinergic neurones the key

There is evidence that the superexpression of the DYRK1A gene may alter the transcription of the DNA (the process that synthesises proteins from DNA). Mr Azkona confirmed the evidence with an experiment with a transgenic mouse which had superexpression. This would directly affect cholinergic neurones and cause damage typical of Down's syndrome with memory and the learning process.

Thus, in the opinion of Mr Azkona, normalising the dose of the DYRK1A gene may be one of the most promising therapeutic strategies in the study of Down's syndrome. Likewise, in his research he has underlined the efficacy of the tapping test, which measures psychomotricity and which was used at the beginning of the process. According to Mr. Azkona, it has been valuable in determining the characteristics of the changes that occur in the visual-spatial memory and of the progress of these changes in persons suffering from the syndrome as they age. This is why he believes that it can also act to detect early neurodegenerative changes and the possible effects of therapy.


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Contact: Amaia Portugal
a.portugal@elhuyar.com
34-943-363-040
Elhuyar Fundazioa
Source:Eurekalert

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