Mice with Alzheimer's disease have their memory restored
The result of the joint work of American and Chinese neuroscientists and chemists was the publication of data according to which compounds of a class that includes several currently used anticancer drugs and synthetic compounds that have not been tested so far effectively restore memory in two animal models of Alzheimer's disease.
According to the head of the study, Professor Yi Zhong, two independent approaches were used in experiments conducted on fruit flies and mice. At the same time, the results obtained with their help do not contradict each other at all.
As a target, the authors chose a receptor for epidermal growth factor (EGFR), the overexpression of which is characteristic of certain types of cancer cells. Two drugs – erlotinib (erlotinib, Tarceva) and gefitinib (gefitinib, Iressa) – are able to significantly, albeit temporarily, suppress the growth of EGFR-positive tumors by blocking this receptor and, accordingly, preventing its activation.
According to the data published by Zhong's group, intracellular signaling mechanisms induced by activation of the EGFR receptor are involved in the development of a poorly studied pathology to date, manifested by memory loss associated with beta-amyloid in patients with Alzheimer's disease.
Previously, scientists studied memory loss associated with beta-amyloid in fruit flies, in whose genome a human gene encoding beta-amyloid-42, which is a specific version of this protein, consisting of 42 amino acids and part of amyloid plaques, was embedded. In behavioral experiments, such fruit flies demonstrate memory disorders similar to those observed in Alzheimer's disease, and are used as a model of this disease.
In the last series of experiments with this model, the authors demonstrated that increased activation of the receptor for the epidermis growth factor in the brain of fruit flies aggravated memory disorders. At the same time, the use of the two antitumor drugs mentioned above during the week completely prevented memory loss by experimental insects. The obtained results were confirmed when working with a mouse model of Alzheimer's disease, also created by embedding the beta-amyloid-42 gene into the human genome.
At the same time, Zhong's Chinese collaborators tested about 2,000 synthetic compounds for activity in relation to beta-amyloid-induced memory loss in fruit flies. Of the 45 identified active compounds, 9 were selected to work with a mouse model of Alzheimer's disease. Four of them showed positive results after application for two months.
Moreover, it turned out that of these four compounds, three, named JKF-006, JKF-011 and JKF-027, not only effectively prevent memory loss in mice, but also prevent beta-amyloid-42-induced activation of the receptor for epidermal growth factor in human cell culture.
Researchers recognize that the pathogenesis of Alzheimer's disease is largely unclear and memory loss may be the result of acute toxic effects of beta-amyloid, manifested independently of degeneration of synapses and neurons. To obtain more complete information, they tested the new approach on middle-aged mice (8 months) with severe memory impairments. At the same time, even short-term use of drugs (for 18 days) restored the memory of animals. However, the authors note that, despite severe memory disorders, these animals had virtually no morphological changes in brain tissue.
The researchers believe that the results are encouraging and hope that in the foreseeable future, the effectiveness of EGFR inhibitors and compounds identified by behavioral tests will be analyzed in clinical trials.
Article by Lei Wang et al. Epidermal growth factor receptor is a preferred target for treating Aß-induced memory loss published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Joslin Diabetes Center:
Scientists reverse Alzheimer’s-like memory loss in animal models by blocking EGFR signaling.
28.09.2012