| First Author | Guha S | Year | 2022 |
| Journal | Brain Behav Immun | Volume | 100 |
| Pages | 194-210 | PubMed ID | 34875346 |
| Mgi Jnum | J:319777 | Mgi Id | MGI:6865363 |
| Doi | 10.1016/j.bbi.2021.11.021 | Citation | Guha S, et al. (2022) ICAM-1 protects neurons against Amyloid-beta and improves cognitive behaviors in 5xFAD mice by inhibiting NF-kappaB. Brain Behav Immun 100:194-210 |
| abstractText | Alzheimer's disease (AD) is mainly characterized by amyloid beta (Abeta) plaque deposition and neurofibrillary tangle formation due to tau hyperphosphorylation. It has been shown that astrocytes respond to these pathologies very early and exert either beneficial or deleterious effects towards neurons. Here, we identified soluble intercellular adhesion molecule-1 (ICAM-1) which is rapidly increased in astrocyte conditioned medium derived from Abeta1-42 treated cultured astrocytes (Abeta1-42-ACM). Abeta1-42-ACM was found to be neuroprotective, however, Abeta1-42-ACM deprived of ICAM-1 was unable to protect neurons against Abeta1-42 mediated toxicity. Moreover, exogenous ICAM-1 renders protection to neurons from Abeta1-42 induced death. It blocks Abeta1-42-mediated PARP cleavage and increases the levels of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, and decreases pro-apoptotic protein Bim. In an Abeta-infused rat model of AD and in 5xFAD mouse, intra-peritoneal administration of ICAM-1 revealed a reduction in Abeta load in hippocampal and cortical regions. Moreover, ICAM-1 treatment led to an increment in the expression of the Abeta-degrading enzyme, neprilysin in 5xFAD mice. Finally, we found that ICAM-1 can ameliorate cognitive deficits in Abeta-infused rat and 5xFAD mouse. Interestingly, ICAM-1 could block the NF-kappaB upregulation by Abeta and inhibition of NF-kappaB recovers cognitive impairments in 5xFAD mice. Thus, our study finds a neuroprotective role of ICAM-1 and suggests that it can be a major candidate in cytokine-mediated therapy of AD. |
