Glucagon-like peptide-1 analogs mitigate neuroinflammation in Alzheimer's disease by suppressing NLRP2 activation in astrocytes.
Mol Cell Endocrinol
; 542: 111529, 2022 02 15.
Article
em En
| MEDLINE
| ID: mdl-34906628
ABSTRACT
Neuroinflammation is closely linked to the pathogenesis of Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) analogs exhibit anti-inflammatory and neuroprotective effects; hence, we investigated whether they reduce cognitive impairment and protect astrocytes from oxidative stress. We found that 5 × FAD transgenic mice treated with the synthetic GLP-1 receptor agonist exenatide had improved cognitive function per the Morris water maze test. Immunohistochemistry, western blotting, and ELISAs used to detect inflammatory factors revealed reduced neuroinflammation in extracted piriform cortexes of exenatide-treated mice as well as lower amyloid ß1-42-induced oxidative stress and inflammation in astrocytes treated with exendin-4 (the natural analog of exenatide). Adenovirus-mediated overexpression of nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 2 (NLRP2) revealed that exenatide/exendin-4 function may be attributed to NLRP2 inflammasome inhibition. Collectively, our results indicate that GLP-1 analogs improve cognitive dysfunction in vivo and protect astrocytes in vitro, potentially via the downregulation of the NLRP2 inflammasome.
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MEDLINE
Assunto principal:
Fármacos Neuroprotetores
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Doença de Alzheimer
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Animals
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En
Ano de publicação:
2022
Tipo de documento:
Article