UNN biologists propose an innovative approach to the treatment of Alzheimer's disease
Researchers at the Institute of Biology and Biomedicine (IBBM) of Lobachevsky University used the drug necrostatin-1 to inhibit necroptosis, one of the types of nerve cell death. Current studies demonstrate that this form of cell death significantly contributes to neuron loss in neurodegenerative processes. The course administration of the drug in aging mice with familial Alzheimer's disease prevented the progression of neurological disorders, maintained normal motor activity levels and the healthy condition of brain tissues.
"Necroptosis is a type of regulated cell death that triggers a strong inflammatory response. The processes leading to cell death unfold in stages, in a cascade manner.The drug blocked these processes at the initial stage.We administered necrostatin-1 to mice starting at six months of age, when the first signs of neurodegeneration and cognitive impairments appear in the animal line we use. After three months of treatment, the mice were trained in a maze to assess their memory, along with other tests. As a result, the animals felt well, learned faster, and memorised the maze better than the control group that did not receive the drug. Moreover, brain tissue damage in these animals was minimal. The therapy substantially slowed down the pathology's progression. Meanwhile, the control group of untreated animals felt progressively worse and were unable to learn or retain information," said Dr. Elena Mitroshina, the study's author, professor at the UNN Department of Neurotechnology.
The scientists note that the treatment was more effective in males than in females, which is attributed to the earlier onset and faster progression of neurodegeneration in females. The researchers plan to develop new treatment protocols considering these differences.
"Nerve cells can regenerate even in adult life, but the rate of their regeneration is lower than the extent of their destruction. By slowing down the rate at which cells die, we can restore this balance. Our studies show that necroptosis is a significant factor in the development of age-related brain pathologies, and necrostatin-1 has the potential to stop the progression of the disease. Currently, this compound is used in scientific research. It can penetrate the blood-brain barrier and enter the brain through intraperitoneal and intravenous administration. If our colleagues from research centres in Russia and around the world achieve similar results, the drug and its analogues could have promising clinical applications, although detailed studies of the drug's effects on cells and an assessment of possible side effects are undoubtedly necessary," noted Elena Mitroshina.
"The work of the IBBM team in the field of neurodegenerative disease therapy demonstrates the university's strong research potential in biomedicine. We are systematically developing areas related to life sciences and human health, and we see this work as one of the key achievements of our research agenda. The results obtained with the support of the Russian Science Foundation provide a solid basis for further clinical studies," said Oleg Trofimov, Rector of Lobachevsky University.
Biologists at Lobachevsky University will need to determine the long-term consequences of necrostatin-1 therapy and investigate the behaviour of surviving brain cells. They plan to conduct experiments with new drug administration protocols. Scientists are interested in how stress will affect the development of neurodegeneration in aged mice and how this will impact the efficacy of the therapy.
The research was conducted as part of a grant from the Russian Science Foundation. The results have been published in the scientific journal Opera Medica et Physiologica. A review article in the international scientific journal Frontiers in Aging Neuroscience outlines the project's initial stage.
