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Sci. Signal., 16 October 2012
Vol. 5, Issue 246, p. pt8
[DOI: 10.1126/scisignal.2003387]


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

Achille Gravanis1,2*, Theodora Calogeropoulou3, Vily Panoutsakopoulou4, Kyriaki Thermos2, Constantinos Neophytou5, and Ioannis Charalampopoulos1,2

1 Foundation of Research and Technology-Hellas (IESL-FORTH), Heraklion, Greece.
2 Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Greece.
3 Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
4 Laboratory of Cellular Immunology, Biomedical Research Foundation, Academy of Athens, Greece.
5 Bionature EA Limited, Nicosia, Cyprus.

A Presentation from the European Society for Paediatric Endocrinology (ESPE) New Inroads to Child Health (NICHe) Conference on Stress Response and Child Health in Heraklion, Crete, Greece, 18 to 20 May 2012.

Abstract: 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.

* Presenter and corresponding author. E-mail: gravanis{at}

Citation: A. Gravanis, T. Calogeropoulou, V. Panoutsakopoulou, K. Thermos, C. Neophytou, I. Charalampopoulos, Neurosteroids and Microneurotrophins Signal Through NGF Receptors to Induce Prosurvival Signaling in Neuronal Cells. Sci. Signal. 5, pt8 (2012).

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