|Manel Esteller, Director of Epigenetics and Cancer Biology , Institute of Biomedical Research of Bellvitge (IDIBELL), with the collaboration of the Institute of Neuropathology IDIBELL led by Isidre Ferrer, have demonstrated for the first time the existence of an epigenetic lesion in the hippocampus of the brain of patients with Alzheimer. The study has been published in the prestigious international journal “Hippocampus”.
Pathologically, Alzheimer ‘s disease is characterized by the accumulation of protein deposits in the brain of patients. These deposits are formed by plates of a protein amyloid-beta and protein tau that when phosphorylated folds as tangles. The root cause of these lesions in most cases is unknown, but specific alterations in regulating genes expression might be involved. So far very few mutations associated with the disease have been reported, and never one that was common to all patients.
“We first started studying 30,000 molecular switches that turn on and off genes in the hippocampal region in the brains of Alzheimer patients in different stages of disease and compared with that of healthy patients of the same age. We note that DUSP22 gene switches off (methylates) as the disease advances” explained Manel Esteller, director of the study.
“But more importantly” continues “was the discovery that this gene regulates tau protein. Perhaps therefore the accumulation of tau protein produced in the brain of patients with Alzheimer results from DUSP22 epigenetic inactivation”. DUSP22 is a dual-specific phosphatase that inhibits PKA and thereby determines tau phosphorylation status.
According Esteller “the finding is relevant not only to determine the causes of the disease, but also to test potential treatments in the future to act on these epigenetic molecular switches”. Currently there is no effective drug treatment for this neurodegenerative condition, existing drugs only slow the progress of the disease.
IDIBELL is a foundation created in 2004 from the merger of several research entities. The centre manages the research of the Bellvitge University Hospital, the Institut Català d’Oncologia (Catalan Institute of Oncology) and the University of Barcelona.
Elena Escubedo (Universitat de Barcelona)