Targeting Adenylate Cyclase: A Novel Concept for Stimulation of Neurogenesis and Pharmacotherapy of Alzheimer's Disease.
Alzheimer's disease
adenylate cyclase
cAMP
cognitive disorders.
neural stem cells
neuroglia
β-amyloid
Journal
Central nervous system agents in medicinal chemistry
ISSN: 1875-6166
Titre abrégé: Cent Nerv Syst Agents Med Chem
Pays: United Arab Emirates
ID NLM: 101269163
Informations de publication
Date de publication:
29 Jul 2024
29 Jul 2024
Historique:
received:
26
01
2024
revised:
21
05
2024
accepted:
10
06
2024
medline:
30
7
2024
pubmed:
30
7
2024
entrez:
30
7
2024
Statut:
aheadofprint
Résumé
The low effectiveness of existing pharmacotherapy strategies for Alzheimer's disease (AD) makes it necessary to develop a new concept for the treatment of this type of dementia. This search is promising to be carried out within the framework of the paradigm of targeting intracellular signaling pathways in Regenerative-Competent Cells (RCCs). The purpose of the research is to study the impact of adenylate cyclase (AC) inhibitor on disorders of the psychoemotional status in aged male C57BL/6 mice, as well as on the dynamics of the content and functioning of RCCs nervous tissue. We examined the effect of the AC inhibitor (2',5'-Dideoxyadenosine) on conditioned reflex activity, behavioral and emotional profile in a mouse AD model (16-month-old (aged) male C57BL/6 mice), as well as the functioning of neural stem cells (NSCs), neuronal-committed progenitors (NCPs), and neuroglial cells in the subventricular zone of the cerebral hemispheres (SVZ). In aged C57BL/6 mice, we found impairments in exploratory behavior, emotional reactivity, and memory, which are the characteristics of senile dementia. Therapy based on AC inhibition led to an increase in the number of NSCs and NPCs in the SVZ due to an increase in their proliferative activity. These changes were more pronounced in NCPs. At the same time, a decrease in the specialization intensity was recorded in NSCs. These phenomena developed against the background of increased secretion of neurotrophic growth factors by oligodendrocytes and microglial cells. The neuroregenerative effects of 2',5'-dideoxyadenosine correlated with the correction of age-related disorders of the psychoemotional status in aged mice. The results provide the basis for the development of targeted drugs based on AC inhibitors to stimulate neurogenesis as an approach for the effective treatment of AD.
Sections du résumé
BACKGROUND
BACKGROUND
The low effectiveness of existing pharmacotherapy strategies for Alzheimer's disease (AD) makes it necessary to develop a new concept for the treatment of this type of dementia. This search is promising to be carried out within the framework of the paradigm of targeting intracellular signaling pathways in Regenerative-Competent Cells (RCCs).
OBJECTIVE
OBJECTIVE
The purpose of the research is to study the impact of adenylate cyclase (AC) inhibitor on disorders of the psychoemotional status in aged male C57BL/6 mice, as well as on the dynamics of the content and functioning of RCCs nervous tissue.
METHODS
METHODS
We examined the effect of the AC inhibitor (2',5'-Dideoxyadenosine) on conditioned reflex activity, behavioral and emotional profile in a mouse AD model (16-month-old (aged) male C57BL/6 mice), as well as the functioning of neural stem cells (NSCs), neuronal-committed progenitors (NCPs), and neuroglial cells in the subventricular zone of the cerebral hemispheres (SVZ).
RESULTS
RESULTS
In aged C57BL/6 mice, we found impairments in exploratory behavior, emotional reactivity, and memory, which are the characteristics of senile dementia. Therapy based on AC inhibition led to an increase in the number of NSCs and NPCs in the SVZ due to an increase in their proliferative activity. These changes were more pronounced in NCPs. At the same time, a decrease in the specialization intensity was recorded in NSCs. These phenomena developed against the background of increased secretion of neurotrophic growth factors by oligodendrocytes and microglial cells. The neuroregenerative effects of 2',5'-dideoxyadenosine correlated with the correction of age-related disorders of the psychoemotional status in aged mice.
CONCLUSION
CONCLUSIONS
The results provide the basis for the development of targeted drugs based on AC inhibitors to stimulate neurogenesis as an approach for the effective treatment of AD.
Identifiants
pubmed: 39076087
pii: CNSAMC-EPUB-141982
doi: 10.2174/0118715249302264240715060630
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
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