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Neuroprotectors

#0312


Modeling of Neurochemical Mechanism of Neurodegenerative Disorders and Development on this Base of Highly Efficient Neuroprotectors.

Tech Area / Field

  • BIO-CHM/Biochemistry/Biotechnology
  • MED-OTH/Other/Medicine

Status
8 Project completed

Registration date
12.12.1994

Completion date
24.10.1999

Senior Project Manager
Urezchenko V M

Leading Institute
Institute of Physiologically Active Substances, Russia, Moscow reg., Chernogolovka

Collaborators

  • Institute of Animal Health, UK, Berkshire\nSt Andrews University / Center for Biomedical Sciences, UK, St Andrews\nUniversität Würzburg / Neuroloishe Klinik, Germany, Würzburg\nUniversität München / Neurologische Klinik, Germany, Munich\nUniversity of Minnesota / Department of Biotechnology and Molecular Biology, USA, MN, Duluth\nSt Elizabeth's Medical Center / Department of Psychiatry, USA, MA, Boston\nCentre d'Etudes du Bouchet, France, Le Bouchet

Project summary

The goal of this project is elaboration of directed neurochemical approach to prevention and pharmacologic correction of a number of spread neurodegenerative diseases (parkinsonism, Alzheimer's Diseases, Huntington's Chorea, amyotrophic lateral sclerosis, etc.) on a basis of the revealed structure-activity relationships in experimental neurotoxicological models.

There are two levels of investigation for attaining this aim. First, it is intended to develop models of neuropathologies, related to degeneration of choline-, glutamate- and monoaminergic neurotransmitters' systems in experimental animals and cell cultures, as well as to investigate molecular mechanisms involved in the progression of pathological processes in vitro with novel selective neurotoxins. Second, directed search and synthesis of new antagonists and modulators of action of model neurotoxins, based on the revealed regularities of neurodegenerative mechanisms.

The practical and fundamental importance of the results obtaining during the progress of this project is determined by the following reasons.

1). Elucidation of the mechanisms related to initiation and development of local group of neurons' degeneration is of interest to theoretical medicine, because it extends our knowledge of ethiopathogeneses of number of abundant neurological disease (Alzheimer's disease, Huntington's chorea, Parkinson's disease, etc.).

2). Elaboration of neurotoxicological models of ND is of great practical interest to modern pharmacology because it provides ground for directed drug design and fast screening of novel promising neuroprotectors in adequate test systems.

3). During the progress of neurotoxicological modeling of ND new biochemical markers of ND could be revealed that might be used in medical diagnostics for early diagnosis of ND.

4). The presence in the environment of chemical hazards structurally related to the neurotoxins studied, determine the practical importance to ecotoxicology of revealing structure-(neuro)activity relationships in number of xenobiotics (in relation to protection from econeurotoxicants that promote the development of neurodegenerative conditions).

Potential role of foreign collaborators is connected with the possibility of the projects results use in the development of the compliment areas of neuroscience related to study of human brain functions and neurodegenerative disorders. Another promising point of collaboration can be connected with the use of ND models, developed in the framework of this project, in the directed search for new efficient neuroactive compounds.


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