A GLP-1/GIP Dual Receptor Agonist DA4-JC Effectively Attenuates Cognitive Impairment and Pathology in the APP/PS1/Tau Model of Alzheimer's Disease.
J Alzheimers Dis
; 83(2): 799-818, 2021.
Article
in En
| MEDLINE
| ID: mdl-34366339
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) is a degenerative disorder, accompanied by progressive cognitive decline, for which there is no cure. Recently, the close correlation between AD and type 2 diabetes mellitus (T2DM) has been noted, and a promising anti-AD strategy is the use of anti-T2DM drugs.OBJECTIVE:
To investigate if the novel glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist DA4-JC shows protective effects in the triple APP/PS1/tau mouse model of AD.METHODS:
A battery of behavioral tests were followed by in vivo recording of long-term potentiation (LTP) in the hippocampus, quantified synapses using the Golgi method, and biochemical analysis of biomarkers.RESULTS:
DA4-JC improved cognitive impairment in a range of tests and relieved pathological features of APP/PS1/tau mice, enhanced LTP in the hippocampus, increased numbers of synapses and dendritic spines, upregulating levels of post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), normalized volume and numbers of mitochondria and improving the phosphatase and tensin homologue induced putative kinase 1 (PINK1) - Parkin mitophagy signaling pathway, while downregulating amyloid, p-tau, and autophagy marker P62 levels.CONCLUSION:
DA4-JC is a promising drug for the treatment of AD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Long-Term Potentiation
/
Neuroprotective Agents
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Diabetes Mellitus, Type 2
/
Glucagon-Like Peptide 1
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Alzheimer Disease
/
Cognitive Dysfunction
/
Disks Large Homolog 4 Protein
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Alzheimers Dis
Journal subject:
GERIATRIA
/
NEUROLOGIA
Year:
2021
Document type:
Article
Affiliation country:
China