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Tactivin Influence on Cells Apoptosis

#3278


Thymic Peptides in the Regulation of Apoptosis of Immunocompetent and Nervous Cells

Tech Area / Field

  • MED-DRG/Drug Discovery/Medicine
  • MED-OTH/Other/Medicine

Status
3 Approved without Funding

Registration date
11.05.2005

Leading Institute
Kolt'sov Institute of Developmental Biology, Russia, Moscow

Supporting institutes

  • Institute of Immunological Engineering, Russia, Moscow reg., Lyubuchany

Collaborators

  • University of Chicago / Pritzker School of Medicine, USA, IL, Chicago\nCNRS / Institut National de la Recherche Agronomique / Centre de Tours, France, Tours\nConstab International, Canada, ON, Toronto\nMedizinische Hochschule Hannover / Neurochirurgische Klinik, Germany, Hannover\nUS Department of Health & Human Services / National Institute of Health / National Cancer Institute / Division of Clinical Sciences, USA, MD, Bethesda

Project summary

The aim of the Project: To study the influence of the thymus and thymic peptides (immunocorrecting preparation Tactivin) on the apoptotic death of haemopoietic (including immunocompetent) and nervous cells, and possible molecular mechanisms of the action of thymic peptides on apoptosis, as well as to isolate molecules affecting apoptosis from a mixture of thymic peptide (Taktivin).

The Project is aimed to solve a fundamental problem of neuro-immunophysiology - functional significance of thymic immunoregulatory peptides in the development of apoptotic death of haemopoietic, including immunocompetent, and nervous cells. The revealing of new properties of thymic peptides will provide a new clinical implication of immunocorrecting drug Tactivin (United States Patent, N 4, 377, 54, 1983) to repair immune system disorders.

Taktivin is widely used for correction of the immune system defects affecting lymphocyte differentiation, selection and maturation. However, presently there is no accurate data revealing the control of apoptosis of immunocompetent and nervous cells by thymus. It is supposed to investigate the Taktivin influence on apoptosis of immunocompetent cells in animal experimental models and in human disorders with up- and down-regulated apoptotic cell death, as well as to evaluate the possible molecular mechanisms of Tactivin effect. Since Tactivin is known to provide detoxication and membrane stabilization as well as to restore mitochondrial functions after the exposure of hard ionizing radiation, a possible influence of the thymus and thymic peptides (Taktivin) on the number of clonogenic stromal cells of haemopoietic organs in fetus and adult animals and on the ability of haemopoietic tissue to regenerate at ectopic transplantation in experimental animals will be investigated. Furthermore, the influence of thymic peptides on the apoptosis of neurons will be studied. The apoptosis in neurons will be induced by neurotoxic substances like 6-hydroxydopamine, widely used to develop an animal experimental model of Parkinson’s disease. The Taktivin influence on the apoptosis of immunocompetent and nervous cells will be also studied in mutant athymic and thymectomated animals characterized by the deficiency of thymic peptides.

New properties of thymic peptides will provide a new clinical implication of Tactivin for correction of apoptosis level in humans. The study of molecular mechanisms of thymic peptide action opens possibilities to search new regulators of apoptotic cell death and to create new drugs for apoptosis correction.


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