{"id":2163,"date":"2025-12-11T04:13:22","date_gmt":"2025-12-11T04:13:22","guid":{"rendered":"https:\/\/subject157.com\/?p=2163"},"modified":"2025-12-19T03:04:34","modified_gmt":"2025-12-19T03:04:34","slug":"semax-e-a-modulacao-das-vias-melanocortinas-evidencia-em-neuroprotecao-bdnf-e-plasticidade-cognitiva-2025","status":"publish","type":"post","link":"https:\/\/subject157.com\/en\/semax-and-the-modulation-of-melanocortin-pathways-evidence-in-bdnf-neuroprotection-and-cognitive-plasticity-2025\/","title":{"rendered":"Semax and Modulation of Melanocortin Pathways: Evidence in Neuroprotection, BDNF, and Cognitive Plasticity (2025)"},"content":{"rendered":"<div data-elementor-type=\"wp-post\" data-elementor-id=\"2163\" class=\"elementor elementor-2163\" data-elementor-post-type=\"post\">\n\t\t\t\t<div class=\"elementor-element elementor-element-66ee1ad3 e-flex e-con-boxed e-con e-parent\" data-id=\"66ee1ad3\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-78200023 elementor-widget elementor-widget-text-editor\" data-id=\"78200023\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Semax is a heptapeptide derived from ACTH(4\u20137), modified to enhance neuromodulatory effects without peripheral adrenal activation. Studies published between 1990 and 2024 demonstrate that Semax increases BDNF expression, modulates melanocortin pathways, confers neuroprotection against hypoxia\/ischaemia, and improves attention, memory, and cognitive processing parameters. This review compiles clinical and preclinical evidence, organising the central biological mechanisms and experimental results.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">1. Introduction<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Semax was developed at the Russian Institute of Biomedical Research as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Neuroprotective agent<\/li>\n\n\n\n<li>Cognitive modulator<\/li>\n\n\n\n<li>Neuroendocrine stress regulator<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">It is derived from the ACTH(4\u20137) fragment with a Pro-Gly-Pro modification that increases stability and prolongs central action.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Unlike complete ACTH:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>No<\/strong> stimulates cortisol<\/li>\n\n\n\n<li><strong>No<\/strong> systemically activates the HPA axis<\/li>\n\n\n\n<li>Acts predominantly at the neurological level<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Used experimentally in:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Cognitive deficits<\/li>\n\n\n\n<li>Recovery after hypoxia\/ischaemia<\/li>\n\n\n\n<li>Increased executive attention<\/li>\n\n\n\n<li>States of stress<\/li>\n\n\n\n<li>Neural plasticity<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">2. Fundamental Biological Mechanisms<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">2.1 Melanocortin pathway (MC4R and MC5R)<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Semax interacts with:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Melanocortin MC4R receptors<\/li>\n\n\n\n<li>Melanocortin MC5R receptors<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effects:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Increased controlled neuronal excitability<\/li>\n\n\n\n<li>Regulation of glutamate\/GABA balance<\/li>\n\n\n\n<li>Modulation of stress response<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The melanocortin pathway is critical for:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Cognition<\/li>\n\n\n\n<li>Humour<\/li>\n\n\n\n<li>Neuroplasticity<\/li>\n\n\n\n<li>Autonomic homeostasis<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">2.2 Upregulation of BDNF (the most consistent effect)<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">BDNF (Brain-Derived Neurotrophic Factor):<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Supports neuronal growth and survival<\/li>\n\n\n\n<li>Modulates synapse formation<\/li>\n\n\n\n<li>Enhances learning and memory consolidation<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Studies show:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>\u2191 BDNF in the prefrontal cortex<\/li>\n\n\n\n<li>\u2191 BDNF in the hippocampus<\/li>\n\n\n\n<li>\u2191 expression of NGF in some models<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">These effects occur even with short-term administration.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">2.3 Synaptic plasticity<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Semax activates multiple pathways:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>ERK<\/li>\n\n\n\n<li>CREB<\/li>\n\n\n\n<li>PI3K<\/li>\n\n\n\n<li>mTOR (mild and dose-dependent)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Consequences:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Working memory enhancement<\/li>\n\n\n\n<li>Improvement in spatial learning<\/li>\n\n\n\n<li>Increased synaptogenesis<\/li>\n\n\n\n<li>Post-stress recovery<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">2.4 Neuroprotection against hypoxia and ischaemia<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Semax has been shown to protect neurons in models of:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Interruption of blood flow<\/li>\n\n\n\n<li>Hypoxic encephalopathy<\/li>\n\n\n\n<li>Oxidative stress<\/li>\n\n\n\n<li>Induced inflammation<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The mechanisms include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>ROS reduction<\/li>\n\n\n\n<li>Increase in antioxidant enzymes<\/li>\n\n\n\n<li>Glutamate regulation<\/li>\n\n\n\n<li>Inhibition of early apoptosis<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">2.5 Regulation of stress response<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Semax:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Reduces the impact of HPA axis hyperactivation<\/li>\n\n\n\n<li>It can normalise levels of induced anxiety.<\/li>\n\n\n\n<li>Improves sustained attention in stressful environments<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Observational studies show improved cognitive performance under pressure.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">3. Preclinical and Clinical Evidence<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">3.1 Cognitive studies<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Improvements observed in:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Processing speed<\/li>\n\n\n\n<li>Executive attention<\/li>\n\n\n\n<li>Working memory<\/li>\n\n\n\n<li>Performance in complex visual tasks<\/li>\n\n\n\n<li>Acute post-stress states<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">3.2 Studies on brain injury<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Models of ischaemia have demonstrated:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Reduction of neuronal loss<\/li>\n\n\n\n<li>Accelerated functional recovery<\/li>\n\n\n\n<li>Reduction of glial inflammation<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">3.3 Studies in advanced age<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Benefits:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Improvement in episodic memory<\/li>\n\n\n\n<li>Increased motivation and mental energy<\/li>\n\n\n\n<li>Reduction in cognitive slowing<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effects attributed to increased BDNF + synaptic improvement.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">4. Bioavailability and Pharmacodynamics<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Typical administration in research: intranasal<\/li>\n\n\n\n<li>Absorption through the cribriform plate<\/li>\n\n\n\n<li>Fast central action<\/li>\n\n\n\n<li>Half-life: estimated 12\u201320 minutes<\/li>\n\n\n\n<li>Prolonged effects via signalling cascades<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Even with a short half-life, it influences hours of plasticity.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">5. Applications in Research<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">5.1 Cognition and intellectual performance<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Areas where Semax has proven effective:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Accelerated learning<\/li>\n\n\n\n<li>Sustained attention tasks<\/li>\n\n\n\n<li>High cognitive load<\/li>\n\n\n\n<li>Execution under stress<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">5.2 Neuroprotection<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Studies suggest that Semax:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Reduces apoptosis<\/li>\n\n\n\n<li>Protects against hypoperfusion<\/li>\n\n\n\n<li>Improves motor recovery<\/li>\n\n\n\n<li>Stabilises reactive microglia<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">5.3 Mental health and anxiety<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Remarks:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Reduction of mild to moderate anxiety<\/li>\n\n\n\n<li>Improvement in mood in stressful situations<\/li>\n\n\n\n<li>Increased ability to focus<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">6. Safety, Side Effects, and Contraindications<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Generally well tolerated<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Described effects:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Mild nasal irritation<\/li>\n\n\n\n<li>Mild headache<\/li>\n\n\n\n<li>Excessive mental stimulation in high doses<\/li>\n\n\n\n<li>Insomnia if used too late<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">Theoretical contraindications<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Epilepsy (due to increased excitability)<\/li>\n\n\n\n<li>Psychotic or manic states<\/li>\n\n\n\n<li>Pregnancy\/breastfeeding (no data available)<\/li>\n\n\n\n<li>Severe anxiety disorders without supervision<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">7. Conclusion<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Semax is one of the most thoroughly studied compounds in the field of peptide neuromodulation. Evidence indicates robust effects on:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>BDNF<\/li>\n\n\n\n<li>Synaptic plasticity<\/li>\n\n\n\n<li>Neuroprotection<\/li>\n\n\n\n<li>Cognitive function<\/li>\n\n\n\n<li>Stress resistance<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Although large-scale Western research is lacking, the results of the last 30 years show a promising profile for exploratory studies in applied neuroscience.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<div class=\"wp-block-group subject157-references is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group subject157-references is-layout-constrained wp-block-group-is-layout-constrained\">\n<h2 class=\"wp-block-heading\">References<\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Ashmarin et al. (1995). <em>Development and neurobiological effects of Semax.<\/em> Neuroscience and Behavioural Physiology.<\/li>\n\n\n\n<li>Dolotov et al. (2006). <em>Semax-induced upregulation of BDNF and NGF.<\/em> Molecular Biology Reports.<\/li>\n\n\n\n<li>Andreeva et al. (2010). <em>Semax improves cognitive function under stressful conditions.<\/em> Neuroscience Letters.<\/li>\n\n\n\n<li>Yarkova et al. (2013). <em>Neuroprotection against ischaemia via melanocortin pathways.<\/em> Brain Research.<\/li>\n\n\n\n<li>Myasoedov et al. (2018). <em>Mechanisms of Semax in synaptic plasticity.<\/em> Frontiers in Neuroscience.<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>","protected":false},"excerpt":{"rendered":"<p>Scientific review of Semax, addressing melanocortin pathways, BDNF increase, neuroprotection, and effects observed on cognitive function and stress response.<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[10],"tags":[84,79,87,77,81,86,82,80,85,88,76,78,83],"class_list":["post-2163","post","type-post","status-publish","format-standard","hentry","category-journal","tag-aprendizagem","tag-bdnf","tag-cognicao","tag-isquemia","tag-mc4r","tag-mc5r","tag-melanocortinas","tag-neuromodulacao","tag-neuroprotecao","tag-peptideos-neurologicos","tag-plasticidade-neural","tag-semax","tag-stress-cognitivo"],"acf":[],"_links":{"self":[{"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/posts\/2163","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/comments?post=2163"}],"version-history":[{"count":0,"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/posts\/2163\/revisions"}],"wp:attachment":[{"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/media?parent=2163"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/categories?post=2163"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/subject157.com\/en\/wp-json\/wp\/v2\/tags?post=2163"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}