GABA-A receptor modulating steroids in acute and chronic stress; relevance for cognition and dementia?
Allopregnanolone
Dementia
GABA-A receptor modulating steroid antagonists
GABA-A receptor modulating steroids
Learning
Memory
Journal
Neurobiology of stress
ISSN: 2352-2895
Titre abrégé: Neurobiol Stress
Pays: United States
ID NLM: 101643409
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
12
09
2019
revised:
13
11
2019
accepted:
18
12
2019
entrez:
11
1
2020
pubmed:
11
1
2020
medline:
11
1
2020
Statut:
epublish
Résumé
Cognitive dysfunction, dementia and Alzheimer's disease (AD) are increasing as the population worldwide ages. Therapeutics for these conditions is an unmet need. This review focuses on the role of the positive GABA-A receptor modulating steroid allopregnanolone (APα), it's role in underlying mechanisms for impaired cognition and of AD, and to determine options for therapy of AD. On one hand, APα given intermittently promotes neurogenesis, decreases AD-related pathology and improves cognition. On the other, continuous exposure of APα impairs cognition and deteriorates AD pathology. The disparity between these two outcomes led our groups to analyze the mechanisms underlying the difference. We conclude that the effects of APα depend on administration pattern and that chronic slightly increased APα exposure is harmful to cognitive function and worsens AD pathology whereas single administrations with longer intervals improve cognition and decrease AD pathology. These collaborative assessments provide insights for the therapeutic development of APα and APα antagonists for AD and provide a model for cross laboratory collaborations aimed at generating translatable data for human clinical trials.
Identifiants
pubmed: 31921942
doi: 10.1016/j.ynstr.2019.100206
pii: S2352-2895(19)30058-X
pii: 100206
pmc: PMC6948369
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100206Subventions
Organisme : NIA NIH HHS
ID : U01 AG031115
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR031986
Pays : United States
Informations de copyright
© 2019 The Author(s).
Déclaration de conflit d'intérêts
The funding sources for this research have not influenced the data presented in this review. TB is a shareholder of Umecrine Cognition AB and has 15 patents in the GAMSA area. RB has four patents or patent applications two in the area of Allopregnanolone treatments.
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