Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression

Abstract Brain-derived neurotrophic factor (BDNF) is involved in the regulation of neuronal cell growth, differentiation, neuroprotection and synaptic plasticity. Although aberrant BDNF/TrkB signaling is implicated in several neurological, neurodegenerative and psychiatric disorders, neurotrophin-ba...

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Autores principales:	L. F. Zainullina, Yu. V. Vakhitova, A. Yu. Lusta, T. A. Gudasheva, S. B. Seredenin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7debdf70a79a45efb7d33c3496c560b5
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spelling	oai:doaj.org-article:7debdf70a79a45efb7d33c3496c560b52021-12-02T14:20:34ZDimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression10.1038/s41598-021-87435-02045-2322https://doaj.org/article/7debdf70a79a45efb7d33c3496c560b52021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87435-0https://doaj.org/toc/2045-2322Abstract Brain-derived neurotrophic factor (BDNF) is involved in the regulation of neuronal cell growth, differentiation, neuroprotection and synaptic plasticity. Although aberrant BDNF/TrkB signaling is implicated in several neurological, neurodegenerative and psychiatric disorders, neurotrophin-based therapy is challenging and is limited by improper pharmacokinetic properties of BDNF. Dimeric dipeptide compound GSB-106 (bis-(N-monosuccinyl-l-seryl-l-lysine) hexamethylenediamide) has earlier been designed to mimic the TrkB-interaction 4 loop of BDNF. It displayed protective effect in various cell-damaging models in vitro. Animal studies uncovered antidepressive and neuroprotective properties upon GSB-106 per os administration. Current study shows that GSB-106 acts similarly to BDNF, promoting survival of serum-deprived neuronal-like SH-SY5Y cells. 100 nmol concentration of GSB-106 provided maximum neurotrophic effect, which corresponds to about 37% of the maximum effect provided by BDNF. Protective properties of GSB-106 arise from its ability to counteract cell apoptosis via activation of TrkB-dependent pro-survival mechanisms, including inactivation of pro-apoptotic BAD protein and suppression of caspases 9 and 3/7. Thus, our study has characterized neurotrophic activity of small dimeric compound GSB-106, which mimics certain biological functions of BDNF and neurotrophin-specific protective mechanisms. GSB-106 also displays similarities to some known low weight peptide and non-peptide TrkB ligands.L. F. ZainullinaYu. V. VakhitovaA. Yu. LustaT. A. GudashevaS. B. SeredeninNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q L. F. Zainullina Yu. V. Vakhitova A. Yu. Lusta T. A. Gudasheva S. B. Seredenin Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression
description	Abstract Brain-derived neurotrophic factor (BDNF) is involved in the regulation of neuronal cell growth, differentiation, neuroprotection and synaptic plasticity. Although aberrant BDNF/TrkB signaling is implicated in several neurological, neurodegenerative and psychiatric disorders, neurotrophin-based therapy is challenging and is limited by improper pharmacokinetic properties of BDNF. Dimeric dipeptide compound GSB-106 (bis-(N-monosuccinyl-l-seryl-l-lysine) hexamethylenediamide) has earlier been designed to mimic the TrkB-interaction 4 loop of BDNF. It displayed protective effect in various cell-damaging models in vitro. Animal studies uncovered antidepressive and neuroprotective properties upon GSB-106 per os administration. Current study shows that GSB-106 acts similarly to BDNF, promoting survival of serum-deprived neuronal-like SH-SY5Y cells. 100 nmol concentration of GSB-106 provided maximum neurotrophic effect, which corresponds to about 37% of the maximum effect provided by BDNF. Protective properties of GSB-106 arise from its ability to counteract cell apoptosis via activation of TrkB-dependent pro-survival mechanisms, including inactivation of pro-apoptotic BAD protein and suppression of caspases 9 and 3/7. Thus, our study has characterized neurotrophic activity of small dimeric compound GSB-106, which mimics certain biological functions of BDNF and neurotrophin-specific protective mechanisms. GSB-106 also displays similarities to some known low weight peptide and non-peptide TrkB ligands.
format	article
author	L. F. Zainullina Yu. V. Vakhitova A. Yu. Lusta T. A. Gudasheva S. B. Seredenin
author_facet	L. F. Zainullina Yu. V. Vakhitova A. Yu. Lusta T. A. Gudasheva S. B. Seredenin
author_sort	L. F. Zainullina
title	Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression
title_short	Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression
title_full	Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression
title_fullStr	Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression
title_full_unstemmed	Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression
title_sort	dimeric mimetic of bdnf loop 4 promotes survival of serum-deprived cell through trkb-dependent apoptosis suppression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7debdf70a79a45efb7d33c3496c560b5
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Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression

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