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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