Registration Number
0222U001098,
0120U101644
, R & D reports
Title
Pharmacological modulation of glutathione-dependent regulation and implementation mechanisms of endogenous neuroprotection and neuroplasticity - a new perspective on neuroprotection in ischemic strokes
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Head
Byelenichev Ihor F., Доктор біологічних наук
Registration Date
24-01-2022
Organization
Zaporizhzhya State Medical University
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The object of study is HSP70/GSH-dependent mechanisms of endogenous neuroprotection in cerebral ischemia.
The purpose of the study – an experimental substantiation of administration of modulators of the glutathione system (glutathione, glutaredoxine and selenium derivatives: Se-glutathione, Se-methionine, Se-cysteine), as well as receptor antagonist of interleukin-1β (RAIL, IL-1Ra) and heat shock factor 1 (HSF-1) in the treatment of stroke based on the basis of experimental data revealing the role of glutathione systems in HSP70-mediated mechanisms of regulation of endogenous neuroprotection.
Research methods – molecular, morphometric, biochemical, histochemical, polymerase chain reaction and immunoblotting.
The results of the Scientific research work and its novelty. For the first time a scientific direction was formed to solve the fundamental problem of pharmacology – the development and production of new drugs for the treatment of cerebrovascular diseases – the complex methodology for creating intranasal systemic drugs with neuroprotective activity in the dosage form of liquid gels was developed.
This is the new and advanced mechanism of RAIL action based on the concept of target neuroprotection. HSP70 blocks the trigger receptors of apoptosis (Fas / Apo-1), inhibits apoptosis in mitochondria at the stage between release of cytochrome C and cleavage of procaspase-9, preventing binding of cytochrome C with the proapoptotic protein Apaf-1 in mitochondria. HSP70 is able to repair oxidatively damaged antioxidant enzymes and transport them from the cytoplasm to other cellular organelles. Increase in expression and/or levels of intracellular HSP70 produces inhibition of transmission of proliferative, apoptotic, inflammatory signals. HSP70 has direct mitoprotective action, and supports the activity of compensatory malate-aspartate shuttle mechanism under conditions of cerebral ischemia, as well as prolongs the action of HIF-1a.
Product Description
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Aliieva Olena Н.
Bak Pavlo H.
Burlaka Bohdan S.
Hanzhuk Yana B.
Zidrashko Halyna A.
Makieieva Liudmyla V.
Parkhomenko Daria P.
Popazova Olena O.
Ryzhenko Viktor P.
Samura Iryna B.
Tykhonovska Maryna A.
Tykhonovskyi Oleksandr V.
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2022-03-09
