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A protein which aggravates Alzheimer's Disease
1/28/14

Following these observations, the researchers decided to begin an in vitro study of cultured mouse neurons in which they over-expressed the ITPKB protein. The results did not disappoint the researchers: a large number of these neurons died and the cell culture supernanant provided evidence of highly increased production of amyloid peptide. 'However, these two things are precisely the particularities of Alzheimer's Disease', specifies Schurmans.

Over-expression does not trigger, but aggravates the disease

What is the effect of ITPKB over-expression in vivo? 'We have created mice which over-express the ITPKB enzyme specifically in the neurons of the hippocampus and the cerebral cortex, i.e. where changes are found in patients affected by Alzheimer's Disease', indicates the researcher. However, this experiment did not yield any particular observations. 'This means that the over-expression of ITPKB alone is insufficient to trigger Alzheimer's Disease and lead to the formation of senile plaques as well as neuron apoptosis', continues Schurmans. 'This enzyme probably does not play a major role in the disease, but may play a regulating role'. 

Far from being discouraged, the researchers over expressed the ITPKB protein in the brain of a genetically-modified mouse which develops an Alzheimer's Disease in less than 6 months. 'And bingo, we see that when we over-express ITPKB in the neurons of the hippocampus and the cortex of these Alzheimer mice, all the characteristics of the disorder are accentuated', reveals the Professor. A large quantity of ITPKB in the tissues involved in Alzheimer's Disease therefore aggravates the disease.

astrogliosis
The role of the ITPKB enzyme is to transform inositol triphosphate (IP3) into inositol tetrakisphosphate (IP4). In this study, published in the journal Brain (1), the researchers also tested the effect of over-expression of a mutated form of the ITPKB enzyme, rendering it inactive. 'These experiments showed that, in this case, the disorder was not aggravated in the mouse', explains Schurmans. 'Importantly, this enzyme therefore catalyses IP4, the product of the reaction. It remains to be seen how IP4 accentuates the characteristics of Alzheimer's Disease.'

(1) V. Stygelbout, K. Leroy, V. Pouillon, K. Ando, E. D’Amico,Y. Jia, H. R. Luo, C. Duyckaerts, C. Erneux, S. Schurmans and J.-P. Brion. Inositol trisphosphate 3-kinase B is increased in human Alzheimer brain and exacerbates mouse Alzheimer pathology. Brain. 2014 Jan 8.

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