RRC ID 82526
Author Tun X, Wang EJ, Gao Z, Lundberg K, Xu R, Hu D.
Title Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer's Disease.
Journal Int J Mol Sci
Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes that ultimately lead to dementia. Currently, 50 million people worldwide suffer from dementia related to AD, and the pathogenesis underlying AD pathology and cognitive decline is unknown. While AD is primarily a neurological disease of the brain, individuals with AD often experience intestinal disorders, and gut abnormalities have been implicated as a major risk factor in the development of AD and relevant dementia. However, the mechanisms that mediate gut injury and contribute to the vicious cycle between gut abnormalities and brain injury in AD remain unknown. In the present study, a bioinformatics analysis was performed on the proteomics data of variously aged AD mouse colon tissues. We found that levels of integrin β3 and β-galactosidase (β-gal), two markers of cellular senescence, increased with age in the colonic tissue of mice with AD. The advanced artificial intelligence (AI)-based prediction of AD risk also demonstrated the association between integrin β3 and β-gal and AD phenotypes. Moreover, we showed that elevated integrin β3 levels were accompanied by senescence phenotypes and immune cell accumulation in AD mouse colonic tissue. Further, integrin β3 genetic downregulation abolished upregulated senescence markers and inflammatory responses in colonic epithelial cells in conditions associated with AD. We provide a new understanding of the molecular actions underpinning inflammatory responses during AD and suggest integrin β3 may function as novel target mediating gut abnormalities in this disease.
Volume 24(6)
Published 2023-3-16
DOI 10.3390/ijms24065697
PII ijms24065697
PMID 36982771
PMC PMC10052535
MeSH Alzheimer Disease* / genetics Animals Artificial Intelligence Cellular Senescence / genetics Inflammation / complications Integrin beta3 / metabolism Mice
Resource
Mice RBRC06344