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Neurosteroids and Microneurotrophins Signal Through NGF Receptors to Induce Prosurvival Signaling in Neuronal Cells

The neurosteroid dehydroepiandrosterone (DHEA) exerts a portion of its neuroprotective effects by directly interacting with the nerve growth factor (NGF) receptors TrkA and p75NTR to induce prosurvival signaling. DHEA is an intermediate in the biosynthesis of estrogens and androgens that affects the endocrine system and potentially increases the risk for developing estrogen- and androgen-dependent tumors. We have synthesized 17-spiro analogs of DHEA that lack estrogenic or androgenic properties and bind to and activate NGF receptors, thus exerting potent neuroprotective effects without the tumor risk. These synthetic DHEA derivatives may serve as lead molecules to develop small agonists of NGF receptors that can penetrate the blood-brain barrier (microneurotrophins) with potential applications in the treatment of neurodegenerative diseases. The neuroprotective properties of microneurotrophins are now being tested in various animal models of neurodegenerative diseases.

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Classifications


Resource Type: Animation, Bibliography, Meeting presentation
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: Achille Gravanis of Foundation of Research and Technology, Heraklion, Theodora Calogeropoulou of National Hellenic Research Foundation, Athens, Vily Panoutsakopoulou of Biomedical Research Foundation, Academy of Athens, Kyriaki Thermos of University of Crete, Heraklion, Constantinos Neophytou of Bionature EA Limited, Cyprus, Ioannis Charalampopoulos of Foundation of Research and Technology-Hellas, Heraklion
Publisher: American Association for the Advancement of Science
Format: application/x-shockwave-flash, text/html
Copyright and other restrictions: Yes
Cost: Yes

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