Neurochemical profiling and brain imaging of a novel neuroprotective compound class, positive allosteric modulators of Sigma-1 receptor

Call Ukrainian-Latvian research project joint call
Implementation period 02.01.2019. – 31.12.2020.
Project partners Latvian Institute of Organic Synthesis (LIOS)
Palladin Institute of Biochemistry (PIB), National Academy of Sciences of Ukraine
Project Leaders Prof. Maija Dambrova (LIOS)
Prof. Tatiana Borisova (PIB NAS of Ukraine)
Costs for Latvian partner 40 000 EUR


The overall aim of the project is pharmacological and neurochemical profiling of a novel class of compounds, positive allosteric modulators (PAM) of Sigma-1 receptor (Sig-1R), in pre-clinical models of spatial and neurodegenerative cognition impairment and investigate possibilities to regulate the interactions of Sigma-1 and NMDA receptors to discover novel treatment means for Alzheimer’s disease.

This aim will be achieved by the implementation of the following objectives:

  1. Assessment of the role of PAMs of Sig-1R in the process of Sig-1 and NMDA receptor interactions, and Sig-1R-related changes in the functioning of presynaptic NMDA receptors;
  2. Analysis of effectiveness of Sig-1R ligands as novel modulators of presynaptic NMDA receptors and dependence of Sig-1R effects on cholesterol content of the plasma membrane of nerve terminals;
  3. Identification of unspecific and toxic effects of known Sig-1R agonists and new Sig-1R positive allosteric modulators in vitro;
  4. Identify the role of PAM of Sig-1R in spatial and neurodegenerative amnesia models in vivo and analyse changes in the expression of Sig-1 and NMDA receptors in brain tissue in amnesic models;
  5. Development of brain imaging methodology (in vivo 3D mice brain tissue images) with polymer-based nanocarriers with unique synthesized near-infrared polymethine/ cyanine dyes and study CNS processes after treatment with the positive allosteric modulators of Sig-1R.

Implementation of this project will lead to discovery of novel pharmaceutical applications of the compounds as well as strengthen the position of Sig-1R as a valuable drug target in CNS pharmacology.