Mice deficient in cystathionine beta synthase display increased Dyrk1A and SAHH activities in brain.

Hyperhomocysteinemia is associated with brain disease. However, biological actions linking hyperhomocysteinemia to neuronal abnormalities are not well understood. We recently found a relationship between Dyrk1A protein expression, a serine/threonine kinase that might be responsible for cognitive functions in Down's syndrome, and hepatic S-adenosylhomocysteine hydrolase (SAHH) activity, which plays a key role in S-adenosylmethionine-dependent methylation reactions. Considering the role of methylation and Dyrk1A in cognitive functions, the aim of this study was to investigate the relationship between Dyrk1A and SAHH activity in brain of hyperhomocysteinemic mice. We found an increase in Dyrk1A protein expression and activity in brain of hyperhomocysteinemic mice, concomitant with an increased SAHH activity. The effect of overexpression of protein Dyrk1A on SAHH activity was confirmed in brain of Dyrk1A transgenic mice, and additionally we found a positive correlation between Dyrk1A and SAHH activity. These observations suggest a potential effect of Dyrk1A on brain phenotypes linked to hyperhomocysteinemia.