Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	ENT-A010, a Novel Steroid Derivative, Displays Neuroprotective Functions and Modulates Microglial Responses
Δημιουργός/Συγγραφέας:	Yilmaz, Canelif Rogdakis, Thanasis Latorrata, Alessia Thanou, Evangelia Karadima, Eleftheria Papadimitriou, Eleni [EL] Σιάπη, Ελένη[EN] Siapi, Eleni Li, Ka Wan [EL] Κατσίλα, Θεοδώρα[EN] Katsila, Theodora [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Charalampopoulos, Ioannis Alexaki, Vasileia Ismini
Ημερομηνία:	2022-03-05
Γλώσσα:	Αγγλικά
DOI:	10.3390/biom12030424
Άλλο:	35327616
Περίληψη:	Tackling neurodegeneration and neuroinflammation is particularly challenging due to the complexity of central nervous system (CNS) disorders, as well as the limited drug accessibility to the brain. The activation of tropomyosin-related kinase A (TRKA) receptor signaling by the nerve growth factor (NGF) or the neurosteroid dehydroepiandrosterone (DHEA) may combat neurodegeneration and regulate microglial function. In the present study, we synthesized a C-17-spiro-cyclopropyl DHEA derivative (ENT-A010), which was capable of activating TRKA. ENT-A010 protected PC12 cells against serum starvation-induced cell death, dorsal root ganglia (DRG) neurons against NGF deprivation-induced apoptosis and hippocampal neurons against Aβ-induced apoptosis. In addition, ENT-A010 pretreatment partially restored homeostatic features of microglia in the hippocampus of lipopolysaccharide (LPS)-treated mice, enhanced Aβ phagocytosis, and increased Ngf expression in microglia in vitro. In conclusion, the small molecule ENT-A010 elicited neuroprotective effects and modulated microglial function, thereby emerging as an interesting compound, which merits further study in the treatment of CNS disorders.
Τίτλος πηγής δημοσίευσης:	Biomolecules
Τόμος/Κεφάλαιο:	12
Τεύχος:	3
Θεματική Κατηγορία:	[EL] Φαρμακευτική[EN] Pharmacy and materia medica [EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	Aβ DHEA ENT-A010 Hippocampus Microglia Neuroprotection Phagocytosis ΤRKA Animals Dehydroepiandrosterone Microglia Signal Transduction Steroids Nerve Growth Factor Neuroprotective Agents
EU Grant:	Horizon 2020 Framework Programme, H2020
EU Grant identifier:	Marie Skłodowska-Curie grant agreement No 765704
Κάτοχος πνευματικών δικαιωμάτων:	© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση με ανοικτή πρόσβαση (link):	https://doi.org/10.3390/biom12030424
Σημειώσεις:	The study was approved by the Landesdirektion, Dresden, Germany (protocol number TVV57/2018, approval 13 December 2018).
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο Άλλα