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The Mitochondrial-Derived Peptides, HumaninS14G and Small Humanin-like Peptide 2, Exhibit Chaperone-like Activity.
Sci Rep
Alan K Okada, Kazuki Teranishi, Fleur Lobo +5 more
Mitochondrial-derived peptides (MDPs) and their analogs have emerged as wide-spectrum, stress response factors protective in amyloid disease models. MDP cytoprotective functions are generally attributed to anti-apoptotic activity, however, little is known about their capacity to facilitate the cell's unfolded protein response via direct interactions with amyloidogenic proteins. Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM). Our thioflavin T fluorescence studies show that HNG inhibits IAPP misfolding at highly substoichiometric concentrations. Seeded fluorescence and co-sedimentation studies demonstrate MDPs block amyloid seeding and directly bind misfolded, seeding-capable IAPP species. Furthermore, our electron paramagnetic resonance spectroscopy and circular dichroism data indicate MDPs do not act by binding IAPP monomers. Taken together our results reveal a novel chaperone-like activity wherein these MDPs specifically target misfolded amyloid seeds to inhibit IAPP misfolding which, along with direct anti-apoptotic activity and beneficial metabolic effects, make HNG and SHLP2 exciting prospects as T2DM therapeutics. These data also suggest that other mitochondrial stress response factors within the MDP family may be amenable to development into therapeutics for protein-misfolding diseases.
Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung diseases.
Pharmacol Ther
Maggie Lam, Simon G Royce, Chrishan S Samuel +1 more
The most common therapies for asthma and other chronic lung diseases are anti-inflammatory agents and bronchodilators. While these drugs oppose disease symptoms, they do not reverse established structural changes in the airways and their therapeutic efficacy is reduced with increasing disease severity. The peptide hormone, relaxin, is a Relaxin Family Peptide Receptor 1 (RXFP1) receptor agonist with unique combined effects in the lung that differentiates it from these existing therapies. Relaxin has previously been reported to have cardioprotective effects in acute heart failure as well anti-fibrotic actions in several organs. This review focuses on recent experimental evidence of the beneficial effects of chronic relaxin treatment in animal models of airways disease demonstrating inhibition of airway hyperresponsiveness and reversal of established fibrosis, consistent with potential therapeutic benefit. Of particular interest, accumulating evidence demonstrates that relaxin can also acutely oppose contraction by reducing the release of mast cell-derived bronchoconstrictors and by directly eliciting bronchodilation. When used in combination, chronic and acute treatment with relaxin has been shown to enhance responsiveness to both glucocorticoids and β2-adrenoceptor agonists respectively. While the mechanisms underlying these beneficial actions remain to be fully elucidated, translation of these promising combined preclinical findings is critical in the development of relaxin as a novel alternative or adjunct therapeutic opposing multiple aspects of airway pathology in lung diseases.
Evaluation of growth hormone-releasing peptide-2 for diagnosis of thyrotropin-producing pituitary adenomas.
Endocr J
Kazunori Kageyama, Satoru Sakihara, Wataru Kameda +4 more
Thyrotropin (TSH)-producing adenomas are a rare cause of hyperthyroidism and are a type of functional pituitary adenoma. The diagnosis of TSH-producing adenoma is a challenging problem in clinical endocrinology. Since growth hormone-releasing peptide-2 (GHRP-2) fails to induce TSH secretion in normal subjects, the effect of GHRP-2 on TSH levels was therefore examined in patients with TSH-producing adenomas. A total of 5 patients (4 women and 1 man) referred to our departments for further evaluation of pituitary hormones were followed-up using the GHRP-2, TSH-releasing hormone (TRH), octreotide, and bromocriptine tests to examine and evaluate TSH secretory dynamics in TSH-producing adenomas. Of 5 patients, 2 (40%) showed such a significant response, defined as a >50% increase in serum TSH level above baseline in the GHRP-2 test. Additionally, 1 patient showed a 48% increase in serum TSH level. In 1 patient whose adenoma was completely removed, basal serum concentrations of TSH were sufficiently suppressed after the operation, and serum TSH levels failed to increase in response to GHRP-2 administration. In 4 patients (80%), a poor response of serum TSH levels was observed in the TRH test. In 2 out of 5 patients (40%), serum TSH levels were significantly decreased following octreotide administration. No patient demonstrated a significant response to the bromocriptine test. In addition to TRH test, the GHRP-2 test as a potential diagnostic tool for TSH-producing pituitary adenomas.
Activity-dependent neuroprotective protein (ADNP) is an alcohol-responsive gene and negative regulator of alcohol consumption in female mice.
Neuropsychopharmacology
Yarden Ziv, Nofar Rahamim, Noa Lezmy +7 more
Neuroadaptations in the brain reward system caused by excessive alcohol intake, lead to drinking escalation and alcohol use disorder phenotypes. Activity-dependent neuroprotective protein (ADNP) is crucial for brain development, and is implicated in neural plasticity in adulthood. Here, we discovered that alcohol exposure regulates Adnp expression in the mesolimbic system, and that Adnp keeps alcohol drinking in moderation, in a sex-dependent manner. Specifically, Sub-chronic alcohol treatment (2.5 g/kg/day for 7 days) increased Adnp mRNA levels in the dorsal hippocampus in both sexes, and in the nucleus accumbens of female mice, 24 h after the last alcohol injection. Long-term voluntary consumption of excessive alcohol quantities (~10-15 g/kg/24 h, 5 weeks) increased Adnp mRNA in the hippocampus of male mice immediately after an alcohol-drinking session, but the level returned to baseline after 24 h of withdrawal. In contrast, excessive alcohol consumption in females led to long-lasting reduction in hippocampal Adnp expression. We further tested the regulatory role of Adnp in alcohol consumption, using the Adnp haploinsufficient mouse model. We found that Adnp haploinsufficient female mice showed higher alcohol consumption and preference, compared to Adnp intact females, whereas no genotype difference was observed in males. Importantly, daily intranasal administration of the ADNP-snippet drug candidate NAP normalized alcohol consumption in Adnp haploinsufficient females. Finally, female Adnp haploinsufficient mice showed a sharp increase in alcohol intake after abstinence, suggesting that Adnp protects against relapse in females. The current data suggest that ADNP is a potential novel biomarker and negative regulator of alcohol-drinking behaviors.
Long days enhance recognition memory and increase insulin-like growth factor 2 in the hippocampus.
Sci Rep
Adriano Dellapolla, Ian Kloehn, Harshida Pancholi +8 more
Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod. Long days enhanced long-term recognition memory, and this effect was abolished by loss of the photopigment melanopsin. Further, long days markedly altered hippocampal clock function and elevated transcription of Insulin-like Growth Factor2 (Igf2). Up-regulation of Igf2 occurred in tandem with suppression of its transcriptional repressor Wilm's tumor1. Consistent with molecular de-repression of Igf2, IGF2 expression was increased in the hippocampus before and after memory training. Lastly, long days occluded IGF2-induced improvements in recognition memory. Collectively, these results suggest that light changes hippocampal clock function to alter memory, highlighting novel mechanisms that may contribute to the positive effects of light. Furthermore, this study provides insight into how the circadian clock can regulate hippocampus-dependent learning by controlling molecular processes required for memory consolidation.
Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity.
Protein Pept Lett
Tatiana V Vyunova, Lioudmila Andreeva, Konstantin Shevchenko +1 more
Anxiety and mood disorders are the most abundant mental health problems worldwide. The commonly used in clinical practice anxiolytics are focused on pharmacological modulation of brain GABA receptor system activity. As a rule, their use presents a wide spectrum of clinical issues such as dependence, memory impairment and etc. There is an increasing appreciation of the role of neuropeptides and bioactive lipids in the pathophysiology of mood and anxiety disorders as "mild" agents. Heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) exhibits prolonged anti-anxiety and nootropic effects.
Effects of Semax on the Default Mode Network of the Brain.
Bull Exp Biol Med
I S Lebedeva, Ya R Panikratova, O Yu Sokolov +4 more
The effects of nootropic drug Semax on the neuronal network of the brain were studied by the resting state functional magnetic-resonance imaging (resting state fMRI). The study was carried out on two groups of healthy volunteers (11 men and 13 women aged 43.9±9.5 years). Resting state fMRI was carried out 3 times: directly before and 5 and 20 min after intranasal 1% Semax (14 subjects) or placebo (10 subjects). The topography of the resting state default mode network was studied. A greater volume of the default mode network rostral (medial frontal cortex) subcomponent was detected in the Semax group in comparison with controls. Resting state fMRI confirmed Semax effects on the neuronal network of the brain and demonstrated topography of these effects.
The octapetide NAP alleviates intestinal and extra-intestinal anti-inflammatory sequelae of acute experimental colitis.
Peptides
Markus M Heimesaat, Eliezer Giladi, Anja A Kühl +2 more
The octapeptide NAP has been shown to exert neuroprotective properties and reduce neuro-inflammatory responses. The aim of the present study was to investigate if NAP provides anti-inflammatory effects in acute murine colitis. To address this, C57BL/6 j mice were challenged with 3.5% dextran sulfate sodium from day 0 until day 6 to induce colitis, either treated intraperitoneally with NAP or placebo (NaCl 0.9%) from day 1 until day 6 post-induction (p.i.) and subjected to in depth macroscopic, microscopic and immunological evaluations. Whereas NAP application did not alleviate macroscopic (i.e. clinical) sequelae of colitis, lower numbers of apoptotic, but higher counts of proliferating/regenerating colonic epithelial cells could be observed in NAP as compared to placebo treated mice at day 7 p.i. Furthermore, lower numbers of adaptive immune cells such as T lymphocytes and regulatory T cells were abundant in the colonic mucosa and lamina propria upon NAP versus placebo treatment that were accompanied by less colonic secretion of pro-inflammatory mediators including IFN-γ and nitric oxide at day 7 p.i. In mesenteric lymph nodes, pro-inflammatory IFN-γ, TNF and IL-6 concentrations were increased in placebo, but not NAP treated mice at day 7 p.i., whereas interestingly, elevated anti-inflammatory IL-10 levels could be observed in NAP treated mice only. The assessed anti-inflammatory properties of NAP were not restricted to the intestinal tract, given that in extra-intestinal compartments such as the kidneys, IFN-γ levels increased in placebo, but not NAP treated mice upon colitis induction. NAP induced effects were accompanied by distinct changes in intestinal microbiota composition, given that colonic luminal loads of bifidobacteria, regarded as anti-inflammatory, "health-promoting" commensal species, were two orders of magnitude higher in NAP as compared to placebo treated mice and even naive controls. In conclusion, NAP alleviates intestinal and extra-intestinal pro-inflammatory sequelae of acute experimental colitis and may provide novel treatment options of intestinal inflammatory diseases in humans.
Structural modification of the tripeptide KPV by reductive "glycoalkylation" of the lysine residue.
PLoS One
Abigael C Songok, Pradip Panta, William T Doerrler +2 more
Peptides that exhibit enzymatic or hormonal activities are regulatory factors and desirable therapeutic drugs because of their high target specificity and minimal side effects. Unfortunately, these drugs are susceptible to enzymatic degradation, leading to their rapid elimination and thereby demanding frequent dosage. Structurally modified forms of some peptide drugs have shown enhanced pharmacokinetics, improving their oral bioavailability. Here, we discuss a novel glycomimetic approach to modify lysine residues in peptides. In a model system, the ε-amine of Ts-Lys-OMe was reductively alkylated with a glucose derivative to afford a dihydroxylated piperidine in place of the amine. A similar modification was applied to H-KPV-NH2, a tripeptide derived from the α-melanocyte stimulating hormone (α-MSH) reported to have antimicrobial and anti-inflammatory properties. Antimicrobial assays, under a variety of conditions, showed no activity for Ac-KPV-NH2 or the α- or ε-glycoalkylated analogs. Glycoalkylated peptides did, however, show stability toward proteolytic enzymes.
The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response.
Curr Mol Pharmacol
Nina Dedic, Alon Chen, Jan M Deussing
Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2.
Microtubule Hyperacetylation Enhances KL1-Dependent Micronucleation under a Tau Deficiency in Mammary Epithelial Cells.
Int J Mol Sci
Haruka Sudo
Enhanced microtubule acetylation has been identified as a negative prognostic indicator in breast cancer. We reported previously that primary cultured human mammary epithelial cells manifest breast cancer-related aneuploidization via the activation of severing protein katanin-like (KL)1 when tau is deficient. To address in this current study whether microtubule hyperacetylation is involved in breast carcinogenesis through mitosis, the effects of tubacin on human mammary epithelial cells were tested using immunofluorescence techniques. Tau-knockdown cells showed enhancement of KL1-dependent events, chromosome-bridging and micronucleation in response to tubacin. These enhancements were suppressed by further expression of an acetylation-deficient tubulin mutant. Consistently, using a rat fibroblast-based microtubule sensitivity test, it was confirmed that KL1 also shows enhanced activity in response to microtubule hyperacetylation as well as katanin. It was further observed in rat fibroblasts that exogenously expressed KL1 results in more micronucleation under microtubule hyperacetylation conditions. These data suggest that microtubule acetylation upregulates KL1 and induces more aneuploidy if tau is deficient. It is thus plausible that microtubule hyperacetylation promotes tumor progression by enhancing microtubule sensitivity to KL1, thereby disrupting spindle microtubules and this process could be reversed by the microtubule-binding and microtubule protective octapeptide NAPVSIPQ (NAP) which recruits tau to the microtubules.
Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone.
Skelet Muscle
Andrea Iskenderian, Nan Liu, Qingwei Deng +15 more
Myostatin antagonists are being developed as therapies for Duchenne muscular dystrophy due to their strong hypertrophic effects on skeletal muscle. Engineered follistatin has the potential to combine the hypertrophy of myostatin antagonism with the anti-inflammatory and anti-fibrotic effects of activin A antagonism.
Ghrelin regulation of glucose metabolism.
Peptides
Anne-Laure Poher, Matthias H Tschöp, Timo D Müller
The a 28-amino acid peptide ghrelin was discovered in 1999 as a growth hormone (GH) releasing peptide. Soon after its discovery, ghrelin was found to increase body weight and adiposity by acting on the hypothalamic melanocortinergic system. Subsequently, ghrelin was found to exert a series of metabolic effects, overall testifying ghrelin a pleiotropic nature of broad pharmacological interest. Ghrelin acts through the growth hormone secretagogue-receptor (GHS-R), a seven transmembrane G protein-coupled receptor with high expression in the anterior pituitary, pancreatic islets, thyroid gland, heart and various regions of the brain. Among ghrelins numerous metabolic effects are the most prominent the stimulation of appetite via activation of orexigenic hypothalamic neurocircuits and the food-intake independent stimulation of lipogenesis, which both together lead to an increase in body weight and adiposity. Ghrelin effects beyond the regulation of appetite and GH secretion include the regulation of gut motility, sleep-wake rhythm, taste sensation, reward seeking behaviour, and the regulation of glucose metabolism. The latter received recently increasing recognition because pharmacological inhibition of ghrelin signaling might be of therapeutic value to improve insuin resistance and type 2 diabetes. In this review we highlight the multifaceted nature of ghrelin and summarize its glucoregulatory action and discuss the pharmacological value of ghrelin pathway inhibition for the treatment of glucose intolerance and type 2 diabetes.
The Safety and Efficacy of Growth Hormone Secretagogues.
Sex Med Rev
John T Sigalos, Alexander W Pastuszak
Growth hormone (GH) increases lean body mass, decreases fat mass, increases exercise tolerance and maximum oxygen uptake, enhances muscle strength, and improves linear growth. Long-term studies of GH administration offer conflicting results on its safety, which has led to strict Food and Drug Administration criteria for GH use. The potential drawbacks of exogenous GH use are believed to be due in part to impaired regulatory feedback.
Analysis of new growth promoting black market products.
Growth Horm IGF Res
Oliver Krug, Andreas Thomas, Helle Malerød-Fjeld +5 more
Detecting agents allegedly or evidently promoting growth such as human growth hormone (GH) or growth hormone releasing peptides (GHRP) in doping controls has represented a pressing issue for sports drug testing laboratories. While GH is a recombinant protein with a molecular weight of 22 kDa, the GHRPs are short (3-6 amino acids long) peptides with GH releasing properties. The endogenously produced GH (22 kDa isoform) consists of 191 amino acids and has a monoisotopic molecular mass of 22,124 Da. Within this study, a slightly modified form of GH was discovered consisting of 192 amino acids carrying an additional alanine at the N-terminus, leading to a monoisotopic mass of 22,195 Da. This was confirmed by top-down and bottom-up experiments using liquid chromatography coupled to high resolution/high accuracy mass spectrometry. Additionally, three analogues of GHRPs were identified as Gly-GHRP-6, Gly-GHRP-2 and Gly-Ipamorelin, representing the corresponding GHRP extended by a N-terminal glycine residue. The structure of these peptides was characterised by means of high resolution (tandem) mass spectrometry, and for Gly-Ipamorelin and Gly-GHRP-2 their identity was additionally confirmed by custom synthesis. Further, established in-vitro experiments provided preliminary information considering the potential metabolism after administration.
Peptide Receptor-Targeted Fluorescent Probe: Visualization and Discrimination between Chronic and Acute Ulcerative Colitis.
ACS Appl Mater Interfaces
Meiying Zeng, Andong Shao, Hui Li +7 more
The inflammatory activity of ulcerative colitis plays an important role in the medical treatment. However, accurate and real-time monitoring of the colitis activity with noninvasive bioimaging method is still challenging, especially in distinguishing between chronic and acute colitis. As a good receptor, the oligopeptide transporter (PepT1) is overexpressed in the colonic epithelial cells of chronic ulcerative colitis, which can deliver tripeptide KPV (Lys-Pro-Val, the C-terminal sequence of α-MSH) into cytosol in the intestine. Herein, we report a PepT1 peptide receptor-targeted fluorescent probe, dicyanomethylene-4H-pyran (DCM)-KPV, with the strategy of conjugating the KPV into the DCM chromophore. The diagnostic fluorescent probe bestows a specific receptor-targeted interaction with PepT1 through the KPV moiety, possessing several beneficial characteristics, such as efficient long emission, low photobleaching, negligible cytotoxicity, and high cytocompatibility in living cells. We build the overexpressed PepT1 on the cytomembrane of ulcerative colitis model Caco-2 cell as the efficient receptor to accumulate the targeted tripeptide KPV in the cytoplasm and nucleus. With the co-localization of DCM-KPV and the DNA-specific fluorophore, DAPI, the specifically long emission from chromophore DCM and efficient receptor-targeted peptide KPV, the fluorescent probe of DCM-KPV makes a breakthrough to the direct noninvasive observation of the accumulation in colon inflammation regions via intestinal mucosa, even successfully distinguishing the chronic, acute ulcerative colitis and normal groups. Compared with the traditional unenhanced magnetic resonance imaging and hematoxylin and eosin (H&E) staining, we make full use of exploiting the specific target-receptor interaction between the tripeptide unit, KPV, and the oligopeptide transporter, PepT1, for sensing selectivity. The desirable diagnostic ability of DCM-KPV can guarantee the real-time tracking and visualization of the role of intracellular KPV on ulcerative colitis, which provides an alternative to replace the time-consuming and tissue sampling-invasive H&E staining diagnosis.
Mitochondrial-Derived Peptides Exacerbate Senescence.
Rejuvenation Res
Andrew R Mendelsohn, James W Larrick
Mitochondrial-derived peptides (MDPs), encoded by mitochondrial DNA, play a cytoprotective role by helping preserve mitochondrial function and cell viability under stressful conditions. Humanin and its homologs and MOTS-c are two of several MDPs hypothesized to have antiaging activity based on correlative studies. For example, humanin plasma levels are inversely correlated with growth hormone and insulin-like growth factor 1 expression, which may promote accelerated aging. Humanin has been shown to protect cells from beta amyloid toxicity and preserve endothelial cell function in a mouse model of atherosclerosis. Furthermore, both humanin and MOTS-c improve insulin sensitivity in mouse models of type 2 diabetes. Recently it was reported that a potent analogue of humanin blocks cardiac fibrosis in aging mice. Although it has been hypothesized that MDPs might have senolytic activity, in a recent report humanin and MOTS-c both exacerbate the senescence-associated-secretory-phenotype (SASP) in senescent cells by stimulating the secretion of IL-6, IL-1β, IL-8, IL-10 and tumor necrosis factor α. It appears that the cytoprotective activity of the MDPs may be permissive for increased expression of a set of proinflammatory cytokines. Given the potential benefits of MDPs in many of the same diseases associated with the presence of senescent cells, a combination of senolytic and MDP-based treatments may be additive or synergistic. The MDPs would protect normal cells, whereas senescent cells would be eliminated by the senolytic therapy. It is even possible that MDPs by increasing the SASP phenotype would make the senescent cells more apt to be cleared by the immune system or more sensitive to senolytics. In contrast, if the MDPs actually cytoprotect the senescent cells, then the treatment can be performed serially with the senolytic used first.
Structural basis of the signal transduction via transmembrane domain of the human growth hormone receptor.
Biochim Biophys Acta Gen Subj
Eduard V Bocharov, Dmitry M Lesovoy, Olga V Bocharova +5 more
Prior studies of the human growth hormone receptor (GHR) revealed a distinct role of spatial rearrangements of its dimeric transmembrane domain in signal transduction across membrane. Detailed structural information obtained in the present study allowed elucidating the bases of such rearrangement and provided novel insights into receptor functioning.
Involvement of the cystathionine-γ-lyase/Cav3.2 pathway in substance P-induced bladder pain in the mouse, a model for nonulcerative bladder pain syndrome.
Neuropharmacology
Maho Tsubota, Yasumasa Okawa, Yuhei Irie +5 more
Hydrogen sulfide (H2S) formed by cystathionine-γ-lyase (CSE) enhances the activity of Cav3.2 T-type Ca2+ channels, contributing to the bladder pain accompanying hemorrhagic cystitis caused by systemic administration of cyclophosphamide (CPA) in mice. Given clinical and fundamental evidence for the involvement of the substance P/NK1 receptor systems in bladder pain syndrome (BPS)/interstitial cystitis (IC), we created an intravesical substance P-induced bladder pain model in mice and analyzed the possible involvement of the CSE/Cav3.2 pathway. Bladder pain/cystitis was induced by i.p. CPA or intravesical substance P in female mice. Bladder pain was evaluated by counting nociceptive behavior and by detecting referred hyperalgesia in the lower abdomen and hindpaw. The isolated bladder tissue was weighed to estimate bladder swelling and subjected to histological observation and Western blotting. Intravesical substance P caused profound referred hyperalgesia accompanied by little bladder swelling or edema 6-24 h after the administration, in contrast to i.p. CPA-induced nociceptive behavior/referred hyperalgesia with remarkable bladder swelling/edema and urothelial damage. The bladder pain and/or cystitis symptoms caused by substance P or CPA were prevented by the NK1 receptor antagonist. CSE in the bladder was upregulated by substance P or CPA, and the NK1 antagonist prevented the CPA-induced CSE upregulation. A CSE inhibitor, a T-type Ca2+ channel blocker and gene silencing of Cav3.2 abolished the intravesical substance P-induced referred hyperalgesia. The intravesical substance P-induced pain in mice is useful as a model for nonulcerative BPS, and involves the activation of the NK1 receptor/CSE/H2S/Cav3.2 cascade.
[Clinical efficacy of neuropeptides in cerebrovascular pathology].
Zh Nevrol Psikhiatr Im S S Korsakova
O A Shavlovskaya
Great value in the treatment of ischemic stroke (IS) is given for neuroprotection. When ischemic neuroprotection aims to increase the period of 'therapeutic window' and stop the cascade of pathological reactions. The neuroprotection is defined as the continuous adaptation of the neuron to new functional conditions, as the key to reducing damage to brain tissue caused by ischemia, it acts at the level of the molecular cascade leading to the dysfunction and death of neurons. Special attention is paid to the study of the properties of low molecular weight neuropeptides that penetrate through the hematoencephalitic barrier and exert a multiple effect on the Central nervous system (CNS) even in small concentrations. One of neuropeptide of cytoprotectors, is Cortexin, containing a complex of low molecular weight peptides (with mass from 1 to 10 kDa), which is optimally balanced and close to the metabolism of brain neurons (organotropic) that exert tissue-specific, regulatory and restorative effect on the cerebral cortex. The article presents data on the effectiveness purpose of Cortexin in patients with IS. It is shown that the optimal scheme for the purpose of Cortexin includes: intramuscular administration of Cortexin in the dose of 20 mg (10 mg morning + 10 mg evening) for 10 days, with a repeat the same course within 10 days after the first, since the first 6 h after the onset of stroke symptoms. The observation period is more than 2 months.