| First Author | Jhamandas JH | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 1 | Pages | 140-9 |
| PubMed ID | 21224052 | Mgi Jnum | J:168237 |
| Mgi Id | MGI:4887495 | Doi | 10.1016/j.ajpath.2010.11.022 |
| Citation | Jhamandas JH, et al. (2011) Actions of beta-amyloid protein on human neurons are expressed through the amylin receptor. Am J Pathol 178(1):140-9 |
| abstractText | Disruption of neurotoxic effects of amyloid beta protein (Abeta) is one of the major, but as yet elusive, goals in the treatment of Alzheimer's disease (AD). The amylin receptor, activated by a pancreatic polypeptide isolated from diabetic patients, is a putative target for the actions of Abeta in the brain. Here we show that in primary cultures of human fetal neurons (HFNs), AC253, an amylin receptor antagonist, blocks electrophysiological effects of Abeta. Pharmacological blockade of the amylin receptor or its down-regulation using siRNA in HFNs confers neuroprotection against oligomeric Abeta-induced caspase-dependent and caspase-independent apoptotic cell death. In transgenic mice (TgCRND8) that overexpress amyloid precursor protein, amylin receptor is up-regulated in specific brain regions that also demonstrate an elevated amyloid burden. The expression of Abeta actions through the amylin receptor in human neurons and temporospatial interrelationship of Abeta and the amylin receptor in an in vivo model of AD together provide a persuasive rationale for this receptor as a novel therapeutic target in the treatment of AD. |
