Against cancer and Alzheimer's disease
Histone deacetylase inhibitors (HDACi) are a group of drugs used as adjuvants in the treatment of various oncological diseases. They increase the effectiveness of chemotherapy and do not have any noticeable side effects. HDACi have also been studied in animal models as cognitive enhancers in psychiatry and neurology. They improved the animals' memory without serious side effects. The mechanism of action of HDACi remained poorly understood.
A research team from the Federal Polytechnic School of Lausanne (EPFL) has shown that the inhibitor HDAC CI-994 (tacedinalin) acts as an aid to epigenetic memory, that is, it supports the ability of cells to read those genes that are important for synaptic transmission, thereby improving communication between neurons. Tacedinalin has virtually no effect on other genes.
Based on Pavlov's conditioning paradigm, the researchers scared mice with electric current as part of an associative memory test. Mice treated with tacedinalin learned fear twice as fast. The experiment was approved by veterinary authorities and classified with a severity of 2.
The authors emphasize that HDACi improve memory only during active learning of something, accelerating the expression of those genes that are already working.
In addition, the team found that tacedinalin acts directly on the epigenome and causes epigenetic changes that support learning. Chromatin – a complex of DNA and histones that pack long DNA molecules into more compact structures – should be available for transcription of synaptic plasticity genes. Indeed, using sequencing technologies, scientists were able to observe that tacedinalin improved the availability of chromatin in genes important for synaptic communication.
Several HDACis are already approved for cancer treatment, meaning they are safe to use in humans. Now they can be retested in clinical trials involving people seeking to improve memory. Currently, two clinical trials are being conducted in Europe, one of which is devoted to the treatment of arachnophobia, and the other to improving memory in patients with Alzheimer's disease.
Article by A.M.Burns et al. The HDAC inhibitor CI-994 acts as a molecular memory aid by facilitating synaptic and intracellular communication after learning is published in the journal PNAS.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EFPL materials: An anti-cancer drug acts as an epigenetic memory aid, scientists find.