ENT-A010, a Novel Steroid Derivative, Displays Neuroprotective Functions and Modulates Microglial Responses.
Aβ
DHEA
ENT-A010
hippocampus
microglia
neuroprotection
phagocytosis
ΤRKA
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
09 03 2022
09 03 2022
Historique:
received:
24
12
2021
revised:
02
03
2022
accepted:
05
03
2022
entrez:
25
3
2022
pubmed:
26
3
2022
medline:
30
4
2022
Statut:
epublish
Résumé
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
Identifiants
pubmed: 35327616
pii: biom12030424
doi: 10.3390/biom12030424
pmc: PMC8946810
pii:
doi:
Substances chimiques
Neuroprotective Agents
0
Steroids
0
Dehydroepiandrosterone
459AG36T1B
Nerve Growth Factor
9061-61-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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