2012/10/16 by Achille Gravanis, Theodora Calogeropoulou, Vily Panoutsakopoulou +3 · 2 citations
Neuroscience · #Nerve injury and regeneration #Neuropeptides and Animal Physiology #Neurogenesis and neuroplasticity mechanisms
paper · doi:10.1126/scisignal.2003387
openalex publication_date 2012/10/16 · openalex created_date 2016/06/24 · openalex updated_date 2026/06/19
The neurosteroid dehydroepiandrosterone (DHEA) exerts a portion of its neuroprotective effects by directly interacting with the nerve growth factor (NGF) receptors TrkA and p75(NTR) 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.