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Mol Nutr Food Res. 2014 Feb;58(2):278-88. doi: 10.1002/mnfr.201300325. Epub 2013 Sep 14.

Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans.

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Human Pharmacology and Clinical Neurosciences Research Group-Neurosciences Program, IMIM-Hospital del Mar Research Institute, Barcelona, Spain; Cardiovascular Risk and Nutrition Research Group-Inflammatory and Cardiovascular Disorders Program, IMIM-Hospital del Mar Research Institute, and CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Barcelona, Spain; University Pompeu Fabra, CEXS-UPF, Barcelona, Spain.



Trisomy for human chromosome 21 results in Down syndrome (DS), which is among the most complex genetic perturbations leading to intellectual disability. Accumulating data suggest that overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), is a critical pathogenic mechanisms in the intellectual deficit.


Here we show that the green tea flavonol epigallocatechin-gallate (EGCG), a DYRK1A inhibitor, rescues the cognitive deficits of both segmental trisomy 16 (Ts65Dn) and transgenic mice overexpressing Dyrk1A in a trisomic or disomic genetic background, respectively. It also significantly reverses cognitive deficits in a pilot study in DS individuals with effects on memory recognition, working memory and quality of life. We used the mouse models to ensure that EGCG was able to reduce DYRK1A kinase activity in the hippocampus and found that it also induced significant changes in plasma homocysteine levels, which were correlated with Dyrk1A expression levels. Thus, we could use plasma homocysteine levels as an efficacy biomarker in our human study.


We conclude that EGCG is a promising therapeutic tool for cognitive enhancement in DS, and its efficacy may depend of Dyrk1A inhibition.


Cognition; DYRK1A; Down syndrome; Epigallocatechin gallate; Homocysteine

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