Time course of the expression of genes of brain-derived neurotrophic factor and nerve growth factor in the hippocampus and frontal cortex induced by semax in rats

Agapova, T. Yu.; Agniullin, Ya. V.; Silachev, Denis N.; Шадрина, М. И.; Сломинский, П. А.; Shram, S. I.; Limborskaya, S. A.; Myasoedov, N. F.

doi:10.3103/s0891416808030063

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…One of these drugs is the synthetic peptide Semax (a fragment of adrenocorticotrophin (ACTH) 4 – 7 conjugated with the C-terminal tripeptide Pro-Gly-Pro), which has been used as a nootropic and neuroprotective drug [ 43 , 44 ]. It has been shown that Semax decreases ischemic brain damage in clinical and animal studies by inducing the expression of neurotrophins and their receptors [ 45 , 46 , 47 , 48 , 49 , 50 ]. Semax contains a fragment of an amino acid sequence critical for the ACTH function but without hormonal activity [ 51 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis

et al. 2021

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The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH(4–7) analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex. Mexidol (100 mg/kg) was administered intraperitoneally, and Semax (25 μg/kg) was administered intranasally, for 7 days each. The expression of PGC-1α and PGC-1α-dependent protein markers of mitochondriogenesis, angiogenesis, and synaptogenesis was measured in the penumbra via immunoblotting at Days 1, 3, 7, and 21 after PT. The nuclear content of PGC-1α was measured immunohistochemically. The suppression of PGC-1α expression was observed in the penumbra from 24 h to 21 days following PT and reflected decreases in both the number of neurons and PGC-1α expression in individual neurons. Administration of Mexidol or Semax was associated with preservation of the neuron number and neuronal expression of PGC-1α, stimulation of the nuclear translocation of PGC-1α, and increased contents of protein markers for PGC-1α activation. This study opens new prospects for the pharmacological modulation of PGC-1α in the ischemic brain.

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Section: Introductionmentioning

confidence: 99%

Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis

et al. 2021

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“…A similar temporal dynamics of the changes in the expression of these two genes was observed within the same brain structures. In addition, two peaks of expression were noted for both genes: the first peak was observed 1.5 h after administration of Semax (Bdnf, 1.38 and 1.32 times in the hippocampus and frontal cortex, respectively; Ngf, 1.38 and 1.11 times, respectively) and the second peak was observed 8 h after administration of Semax (Bdnf, 1.75 and 1.64 times in the hippocampus and frontal cortex, respectively; Ngf, 1.67 and 1.65 times, respectively) [95].…”

Section: Effect Of Semax On Gene Transcriptionmentioning

confidence: 98%

A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides

Kolomin¹,

Шадрина²,

Slominsky³

et al. 2013

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Natural regulatory peptides are biologically active compounds that are produced by various cells and provide a link among the main regulatory systems of the body. The field of research into the biologic activity of endogenous regulatory peptides is extremely vast. These peptides affect the cardiovascular, immune, reproductive, endocrine, digestive, and other systems, alter energy metabolism, and are especially effective in the regulation of the central nervous system. Despite of the wide range of preventive and therapeutic effects of natural regulatory peptides and proteins, their application in clinical practice is difficult. This is primarily because of their extreme instability, as they are rapidly degraded by proteases of the gastrointestinal tract, blood, cerebrospinal fluid, and other biologic media. Compounds with higher stability (i.e., a considerably longer half-life compared with that of natural molecules) and the ability to provide a directional effect on the various body systems were obtained from modifications of endogenous regulatory peptides. Synthetic analogs of regulatory peptides, as a rule, contain only natural amino acids in their composition, and their biodegradation does not lead to the formation of toxic products; thus, they have fewer side effects. This review focuses on the consideration of two synthetic regulatory peptides, Semax and Selank, which were the bases for the creation of new drugs that are used effectively in the treatment of various diseases of the nervous system. The synthetic analog of an adrenocorticotropic hormone 4-10 fragment (ACTH 4-10) Semax is a powerful neuroprotective agent that is particularly effective as a therapy for stroke. Selank was synthesized on the basis of the natural immunomodulator tuftsin. Selank is a powerful anxiolytic that is used as a therapy for generalized anxiety disorder and neurasthenia without sedative and muscle-relaxant effects. This review presents the results of research aimed at studying the influence of these peptides on the transcriptome of brain cells. The problems of drugs developed based on the clinical activities of Semax and Selank are discussed separately.

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“…The maximum increase in gene expression was observed at 30 min after drug administration: Bdnf expression increased by eightfold and Ngf expression by fivefold. Further studies entailed an in vivo analysis of the effect of Semax on the expression levels of Ngf and Bdnf in different parts of the rat brain 21‐25 . Semax treatment had different effects on the activity of these genes in different regions.…”

Section: Analysis Of Gene Expression Under the Action Of Peptides: Frmentioning

confidence: 99%

Pharmacotranscriptomics of peptide drugs with neuroprotective properties

Dergunova

Filippenkov

Limborska

et al. 2020

Medicinal Research Reviews

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Here we present a review of studies on the effects of peptides with neuroprotective properties on gene transcription in nerve cells. The few published works in this area clearly demonstrate massive changes in cell transcriptomes induced by peptides under normal conditions and under conditions of experimental brain ischemia. These changes significantly affect signaling and metabolic pathways, affecting various body systems and confirming the multiple target actions of peptides. The importance of noncoding RNAs in the regulation of these processes is shown, and we discuss the prospects of research for determining the main mechanisms of peptide regulation, which is necessary for the further development of drugs with targeted neuroprotective effects.

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Time course of the expression of genes of brain-derived neurotrophic factor and nerve growth factor in the hippocampus and frontal cortex induced by semax in rats

Cited by 4 publications

References 19 publications

Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis

Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis

A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides

Pharmacotranscriptomics of peptide drugs with neuroprotective properties

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