| Qualified type: | Scientific journal article |
| Title: | ENT-A010, a Novel Steroid Derivative, Displays Neuroprotective Functions and Modulates Microglial Responses |
| Creator: | 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 |
| Date: | 2022-03-05 |
| Language: | English |
| DOI: | 10.3390/biom12030424 |
| Other: | 35327616 |
| Abstract: | 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. |
| Reference title: | Biomolecules |
| Volume/Chapter: | 12 |
| Issue: | 3 |
| Subject: | [EL] Φαρμακευτική[EN] Pharmacy and materia medica
[EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology
[EL] Βιολογία (Γενικά)[EN] Biology (General) |
| Keywords: | Aβ
DHEA
ENT-A010
Hippocampus
Microglia
Neuroprotection
Phagocytosis
ΤRKA
Animals
Dehydroepiandrosterone
Microglia
Signal Transduction
Steroids
Nerve Growth Factor
Neuroprotective Agents |
| Funding stream: | Horizon 2020 Framework Programme, H2020 |
| Identifier of funding stream: | Marie Skłodowska-Curie grant agreement No 765704 |
| Rights holder: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. |
| Rights terms of use: | 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/). |
| Open access link: | https://doi.org/10.3390/biom12030424 |
| Notes: | The study was approved by the Landesdirektion, Dresden, Germany (protocol number TVV57/2018, approval 13 December 2018). |
| Appears in Collections: | Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο
|
