Laboratory of Molecular Neurodegeneration

Laboratory of Molecular Neurodegeneration (LMN) was officially established in December 2012. LMN is a part of organizational structure of R&E Centre “Fundamental basis of medical and biomedical technologies” in the scientific sector of Peter the Great St. Petersburg Polytechnic University (SPbPU) and it is headed by Iliya B. Besprozvanny.

LMN’s team consists mainly of young highly qualified professionals (the total number of employees who have done international and domestic internship with the purpose of training in their direction of research in the period of 2011-2015 is more than 19 people). Theit average age at the moment is not more 35 years. Established thanks to mega grant financing for the project 11.G34.31.0056 the laboratory was one of the growth points for the development of research in the field of neurodegenerative diseases in St. Petersburg in Russia. The laboratory is actively assisting in training world-class professionals.

LMN is fully integrated in the educational structure of the Polytechnic University. In its premises the following works are performed: bachelor final papers, master’s theses in the Master Degree program “Neurobiological Engineering” (Program Head – Iliya B. Besprozvanny) as well as post-graduate theses performed by students of the department “Medical Physics” of SPbPU Institute of Physics, Nanotechnology and Telecommunications (since 2014 Iliya B. Besprozvanny has been the Head of the Department). So since 2011 the following specialists were trained: 5 graduates with master degrees, 1 BA and 4 higher qualification researches, including 3 PhD specialists and 1 DSc. Training such professionals does not only raise the level of fundamental research activities in St. Petersburg and in Russia, but as well contributes to the development of the pharmaceutical and biotechnology sectors.

Main research topics of the laboratory are connected with molecular mechanisms of the origin and development of neurodegenerative diseases such as Alzheimer’s disease (AD), Huntington’s disease (HD) and spinal cerebellar ataxia (SCA). These diseases represent a medical, social, economic and scientific problem of extreme importance. Medicine used to treat diseases affect the brain, have a limited effect, bringing only temporary relief in the manifestation of disease symptoms or retention in the course of the disease. Such a situation, first of all, is due to the lack of understanding of the mechanisms responsible for these diseases. To solve this problem, Professor Iliya B. Besprozvanny previously put forward a “calcium hypothesis” of neurodegenerative diseases, which says: breach of the ability of neurons to control the intracellular calcium ion concentration is one of the main causes for the beginning and development of neurodegenerative diseases. This hypothesis also suggests that drugs capable of normalizing calcium signalling may be useful for the treatment of these diseases. Experimental work of LMN staff aimed at further development and testing of “calcium hypothesis” and search and testing of modulators of calcium channel activity.

The following most important results were gained thanks to the research work:

1. disturbances in function of store-operated calcium channels found in AD and HD. Based on the findings new potential target proteins have been proposed for the development of new medicines. Chemical compounds were found to be prototypes of medicine capable of normalizing the function of the store-operated channels in cellular and animal models of AD and HD. Research of potential medicine for the treatment of AD was transferred to the stage of preclinical testing;
2. in collaboration with the biotech company Ataxion the beneficial effects of new medicine were demonstrated in preclinical models of spinal cerebellar ataxia, type 2 (STIM2). On the basis of electrophysiological and pharmacodynamics data and pharmacokinetics the leading compound was selected of the future development of the therapeutic agent of ataxia;
3. advances methodology for the control of the functional activity of nerve cells based on optogenetics method have been. This methodology allows to control the function of individual neurons both in the cells culture and in the whole animal. This methodology began to be used widely by foreign scientists in the past few years. In Russia, this methodology is of great interest as well.

All the results have been published in top ranking medical journals. In the period of 2011 -2015 the head and members of the research team published 36 articles with an average impact factor of 4.01, such as “Reduced Synaptic STIM2 Expression and Impaired Store -Operated Calcium Entry Cause Destabilization of Mature Spines in Mutant Presenilin Mice”, Suya Sun, Hua Zhang, Jie Liu, Elena Popugaeva, Nan-Jie Xu, Stefan Feske, Charles L. White, III, and Ilya Bezprozvanny (2014), Neuron, vol 82, pp 79-93., the impact factor of 16,0, «STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity», Elena Popugaeva, Ekaterina Pchitskaya, Anastasiya Speshilova, Hua Zhang, Olga Vlasova, Sergey Alexandrov and Ilya Bezprozvanny (2015 ), Journal of Molecular Neurodegeneration, 10:37, the impact factor of 6,563, etc. Also, the results were presented to members of the research team in 9 international and 13 Russian scientific conferences, seminars and symposia.

As a result of new mechanisms have been discovered as responsible for age-related changes in calcium signaling in different compartments of neurons in models of neurodegenerative diseases, in transgenic mice lines AD, HD and STIM2. These fundamental results provided an opportunity to identify the specific target for developing new medicine.

In the course of LMN work in the direction of research members of the scientific team eceived and registered intellectual property in the form of 3 know-how, won 16 grants, including grants for young biologists of Dynasty Foundation, for students, PhDs, of Federal special purpose programme and nonprofit charitable organization ” Vladimir Potanin Charity Foundation”, Russian Science Foundation, etc. Works were carried out under the guidance of the research team members. Laboratory staff is involved in the implementation of 5 commercial works in the direction of research, as well as they organized and carried out more than 4 scientific schools and conferences.