An investigation reveals a new approach to the treatment of Alzheimer's that could reverse the loss of memory of the last stages of this disease.
The team, led by scientists from the University of Buffalo (United States), has discovered that, by focusing on genetic changes caused by epigenetic influences, different from DNA sequences, it is possible to reverse the Impairment of memory in an Alzheimer's animal model.
The key is to control levels of an enzyme to restore damaged receptors due to the disease and prevent the operation of brain connections involved in short-term memory.
"In this study, we not only identify the factors that contribute to the loss of memory, but also find ways to reverse them temporarily," explains in a statement Zhen Yan, professor of the Department of Physiology and Biophysics of the Faculty of Medicine and Jacobs Biomedical Sciences at the University of Buffalo.
The research was carried out on mouse models with genetic mutations of Alzheimer's family, an inherited modality of this disease. Post-mortem brain tissues of Alzheimer's patients were also observed.
Alzheimer's is linked to epigenetic anomalies
Alzheimer's is genetic and environmental risk factors, such as aging, which are combined to produce epigenetic changes, translated into modifications in gene expression. For now, little is known about how this happens.
Alzheimer's epigenetic changes occur mainly in advanced stages, when patients can not retain recently-learned information and exhibit the most dramatic cognitive decline, Yan explains.
A key reason for cognitive impairment is the loss of glutamate receptors, receptor molecules of the main excitatory neurotransmitter of the brain, which are critical for learning and short-term memory.
"We discovered that, in Alzheimer's disease, many subunits of glutamate receptors in the brain's frontal cortex are regulated in the lower part, interrupting the excitatory signals, which affects the work memory," he said. Yan explains.
The researchers also discovered that the loss of glutamate receptors is the result of an epigenetic process known as "repressive modification of histones", which is greater in patients with Alzheimer's disease. He was observed both in animal models that they studied and in the post-mortem weave of Alzheimer's patients.
Histone modifiers change the chromatin structure, which controls the access of the genetic material to the transcriptional machinery of a cell. "This abnormal modification of Alzheimer's histone is what represses gene expression, decreasing glutamate receptors, which leads to loss of synaptic function and memory deficits," Yan explains. .