“The inhibition of DREAM could improve Huntington disease”, said Dr. José Ramón Naranjo from the Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB-CSIC), in his seminar “DREAM: interactions, targets and functions” at the Hospital Duran i Reynals last July 6th.
DREAM is a transcriptional repressor in the nucleus and regulates the traffic of potassium (K+) and calcium (Ca+2) through the interaction with specific channels for these ions. “We prepare transgenic mice overexpressing a constitutively active mutant DREAM (daDREAM). Genome-wide analysis of the hippocampus from these mice showed that DREAM was involved in activity-dependent gene expression in the hippocampus and by hence it is important in learning and memory”, said Dr. Naranjo.
DREAM directly regulates basal and induced expression of the “so called” immediate early genes that regulate other genes. Thus, DREAM regulates the on/off switching of several activity-dependent transcriptional cascades in neurons that control synaptic plasticity, learning and memory. Since DREAM regulates Ca2+-dependent gene expressions and homeostasis, DREAM might be important in Huntington Disease (HD) that affects middle-aged people.
DREAM and Huntington Disease
HD is a genetic disease produced by the mutation of the huntingtin gene (mHtt). Expression of mHtt largely modifies gene expression and has a specific effect on genes related to Ca2+ homeostasis. This effect has been observed both in human patients as well as in mouse models of the disease.
“We try to answer if the expression of endogenous DREAM was modified in murine models of HD”, said the researcher. “We found an early decrease in DREAM expression in peripheral tissues in these mice. Moreover, genetic evidences indicate that DREAM regulates the onset and progression of HD in animal models of the disease. Thus, pharmacological inhibition of DREAM may represent a new target for the treatment of this neurological disease.
Blockers of DREAM activity, new therapeutically strategy in HD
These results suggest that treatment with blockers of DREAM activity could represent a new therapeutic strategy in HD.