Synthetic Microneurotrophins: neurotrophin receptor modulators for therapeutics of neurodegenerative diseases

Synthetic Microneurotrophins: neurotrophin receptor modulators for therapeutics of neurodegenerative diseases | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL British Journal of Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 5 March 2025 V1 Latest version Share on Synthetic Microneurotrophins: neurotrophin receptor modulators for therapeutics of neurodegenerative diseases Authors : Achilleas Gravanis [email protected] , ioanna Zota , Theodora Calogeropoulou , konstantina Chanoumidou , and ioannis Charalampopoulos Authors Info & Affiliations https://doi.org/10.22541/au.174118705.51612892/v1 372 views 320 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Neurodegenerative disorders are characterized by the chronic progressive degeneration of specific neuronal subtypes, neuroinflammation, myelin damage and synaptic loss. Despite their growing incidence, advancements in effective treatments remain limited, due to lack of knowledge for the etiology of the diverse pathophysiology to design systematic therapies. Several studies highlight the role of neurotrophic factors (NTFs) as potential neuroprotective, regenerative therapies for these disorders. Although NTFs hold protective and regenerative potential for chronic neuroinflammatory and neurodegenerative conditions, major hurdles impair their clinical use, such as optimizing the dosage of NTFs, minimizing the invasiveness of delivery methods, overcoming blood-brain barrier impermeability and managing side effects. The last two decades our group synthesized and screened a large chemical library of steroidal analogs of Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, for their ability to mimic neurotrophin neuroprotective and neurogenic actions. Interestingly, DHEA was shown to interact with all neurotrophin receptors, acting most probably as an ancestral neurotrophin early in evolution. However, its chronic pharmacological use is questioned by its action as a major precursor of steroidogenesis. This review highlights the findings of numerous preclinical studies on these synthetic, non-toxic, blood-brain barrier permeable DHEA derivatives, named microneurotrophins (MNTs), deprived of endocrine actions, activators of specific neurotrophin receptors. The multimodal actions of MNTs against neuronal death and activation of microglia, in addition to their beneficial effects in synaptogenesis and neurogenesis, place them as interesting lead molecules in the armamentarium of therapeutics for neurodegeneration. Supplementary Material File (gravanis invited review brjpharmacol.pdf) Download 1.18 MB Information & Authors Information Version history V1 Version 1 05 March 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Collection British Journal of Pharmacology Keywords neurodegeneration/neuroprotection receptor theory small molecules Authors Affiliations Achilleas Gravanis [email protected] University of Crete Medical School View all articles by this author ioanna Zota University of Crete School of Medicine View all articles by this author Theodora Calogeropoulou National Hellenic Research Foundation Institute of Biology Medicinal Chemistry and Biotechnology View all articles by this author konstantina Chanoumidou University of Crete School of Medicine View all articles by this author ioannis Charalampopoulos University of Crete School of Medicine View all articles by this author Metrics & Citations Metrics Article Usage 372 views 320 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Achilleas Gravanis, ioanna Zota, Theodora Calogeropoulou, et al. Synthetic Microneurotrophins: neurotrophin receptor modulators for therapeutics of neurodegenerative diseases. Authorea . 05 March 2025. DOI: https://doi.org/10.22541/au.174118705.51612892/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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