| First Author | Kitazawa M | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 12 | Pages | 6539-49 |
| PubMed ID | 22095718 | Mgi Jnum | J:180375 |
| Mgi Id | MGI:5306178 | Doi | 10.4049/jimmunol.1100620 |
| Citation | Kitazawa M, et al. (2011) Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal beta-catenin pathway function in an Alzheimer's disease model. J Immunol 187(12):6539-49 |
| abstractText | Inflammation is a key pathological hallmark of Alzheimer's disease (AD), although its impact on disease progression and neurodegeneration remains an area of active investigation. Among numerous inflammatory cytokines associated with AD, IL-1beta in particular has been implicated in playing a pathogenic role. In this study, we sought to investigate whether inhibition of IL-1beta signaling provides disease-modifying benefits in an AD mouse model and, if so, by what molecular mechanisms. We report that chronic dosing of 3xTg-AD mice with an IL-1R blocking Ab significantly alters brain inflammatory responses, alleviates cognitive deficits, markedly attenuates tau pathology, and partly reduces certain fibrillar and oligomeric forms of amyloid-beta. Alterations in inflammatory responses correspond to reduced NF-kappaB activity. Furthermore, inhibition of IL-1 signaling reduces the activity of several tau kinases in the brain, including cdk5/p25, GSK-3beta, and p38-MAPK, and also reduces phosphorylated tau levels. We also detected a reduction in the astrocyte-derived cytokine, S100B, and in the extent of neuronal Wnt/beta-catenin signaling in 3xTg-AD brains, and provided in vitro evidence that these changes may, in part, provide a mechanistic link between IL-1 signaling and GSK-3beta activation. Taken together, our results suggest that the IL-1 signaling cascade may be involved in one of the key disease mechanisms for AD. |
