Recent Research on Dimeric Dipeptide Mimetics of NGF and BDNF Are Promising Agents for PostStroke Therapy

Recent Research on Dimeric Dipeptide Mimetics of NGF and BDNF Are Promising Agents for PostStroke Therapy

The dimeric dipeptide mimetics of the brain derived neurotrophic factor (BDNF) loops 1, 2 and 4 and
nerve growth factor (NGF) loop 4 were designed and synthesized at the Zakusov Research Institute
of Pharmacology. All of the obtained compounds activated a corresponding specific NGF or BDNF
tyrosine kinase receptor (TrkA or TrkB), but had different postreceptor signaling patterns. GSB-106
activated the ERK and AKT, whereas GSB-214 and GK-2 only activated the AKT kinase. Here we
report a comparative analysis of neuroprotective activity of these dipeptides in a model of ischemic
stroke induced by transient middle cerebral artery occlusion (MCAO). In the experiment with BDNF
mimetics, GSB-106 reduced this volume by 66% and GSB-214 by 26%. NGF mimetic GK-2 reduced
the cerebral infarct volume by 45%. Thus, BDNF mimetic, which activated both the ERK and AKT,
and NGF mimetic, which selectively activated PI3K/AKT, showed high neuroprotective efficacy. In
addition, we studied neuroprotective effects of GK-2 at the beginning of the treatment 6, 8 and 24
hours after reperfusion. The neuroprotective effect of GK-2 persisted in all these conditions. The
effectiveness of GK-2 at a delayed start of administration suggests that the dipeptide has
neuroregenerative properties. The results obtained suggest a potential role for the dimeric dipeptide
NGF and BDNF mimetics as therapeutic agents useful in the treatment of a stroke.

Author (s) Details

Polina Povarnina
Department of Medicinal Chemistry, Federal State Budgetary Institution “Research Zakusov Institute of Pharmacology”, Moscow, Russia.

Tatyana A. Gudasheva
Department of Medicinal Chemistry, Federal State Budgetary Institution “Research Zakusov Institute of Pharmacology”, Moscow, Russia.

Sergey B. Seredenin
Department of Pharmacogenetics, Federal State Budgetary Institution “Research Zakusov Institute of Pharmacology”, Moscow, Russia.

View Book :- https://bp.bookpi.org/index.php/bpi/catalog/book/264

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