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Despite their growing incidence, advancements in effective treatments remain limited, because of lack of knowledge for the aetiology 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 optimising the dosage of NTFs, minimising the invasiveness of delivery methods, overcoming blood\u2010brain\u2010barrier (BBB) impermeability and managing side effects. In the last two decades our group have synthesised and screened a large chemical library of steroidal analogues of <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=2370\">dehydroepiandrosterone<\/jats:ext-link> (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\u2010toxic, BBB permeable DHEA derivatives, named microneurotrophins (MNTs), deprived of endocrine actions, activators of specific neurotrophin receptors. 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