|  Help  |  About  |  Contact Us

Publication : Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer's disease.

First Author  Tan MS Year  2014
Journal  Cell Death Dis Volume  5
Issue  8 Pages  e1382
PubMed ID  25144717 Mgi Jnum  J:351732
Mgi Id  MGI:7663100 Doi  10.1038/cddis.2014.348
Citation  Tan MS, et al. (2014) Amyloid-beta induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer's disease. Cell Death Dis 5(8):e1382
abstractText  Increasing evidence has shown the aberrant expression of inflammasome-related proteins in Alzheimer's disease (AD) brain; these proteins, including NLRP1 inflammasome, are implicated in the execution of inflammatory response and pyroptotic death. Although current data are associated NLRP1 genetic variants with AD, the involvement of NLRP1 inflammasome in AD pathogenesis is still unknown. Using APPswe/PS1dE9 transgenic mice, we found that cerebral NLRP1 levels were upregulated. Our in vitro studies further showed that increased NLRP1-mediated caspase-1-dependent 'pyroptosis' in cultured cortical neurons in response to amyloid-beta. Moreover, we employed direct in vivo infusion of non-viral small-interfering RNA to knockdown NLRP1 or caspase-1 in APPswe/PS1dE9 brain, and discovered that these NLRP1 or caspase-1 deficiency mice resulted in significantly reduced neuronal pyroptosis and reversed cognitive impairments. Taken together, our findings indicate an important role for NLRP1/caspase-1 signaling in AD progression, and point to the modulation of NLRP1 inflammasome as a promising strategy for AD therapy.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

4 Bio Entities

0 Expression