ArticleBrain sciences2021
AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.
Article in Brain sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
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- Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain Injury.Neurotrauma reports · 2025Article
- Diminazene Ameliorates Neuroinflammation by Suppression of Astrocytic miRNA-224-5p/NLRP3 Axis in Alzheimer's Disease Model.Journal of inflammation research · 2023Article
- Impact of the Renin-Angiotensin System on the Pathogeny and Pharmacotherapeutics of Neurodegenerative Diseases.Biomolecules · 2022Review
- Potential bioactive compounds and mechanisms ofFrontiers in aging neuroscience · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer's disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory in previous studies. In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice. We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group. Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test. Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining. Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10. Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice. These findings highlight the brain AngIV/PI3K/AKT axis as a potential target for the treatment of AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.