QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 16, 2004, 24(24):5579-5584; doi:10.1523/JNEUROSCI.1051-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Jhamandas, J. H. Articles by MacTavish, D. Search for Related Content PubMed PubMed Citation Articles by Jhamandas, J. H. Articles by MacTavish, D.

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Antagonist of the Amylin Receptor Blocks -Amyloid Toxicity in Rat Cholinergic Basal Forebrain Neurons

Jack H. Jhamandas and David MacTavish

Division of Neurology, Department of Medicine, Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, Alberta T6G 2S2, Canada

Salvage of cholinergic neurons in the brain through a blockade of the neurotoxic effects of amyloid protein (A) is one of the major, but still elusive, therapeutic goals of current research in Alzheimer's disease (AD). To date, no receptor has been unequivocally identified for A. Human amylin, which acts via a receptor composed of the calcitonin receptor-like receptor and a receptor-associated membrane protein, possesses amyloidogenic properties and has a profile of neurotoxicity that is strikingly similar to A. In this study, using primary cultures of rat cholinergic basal forebrain neurons, we show that acetyl-[Asn30, Tyr32] sCT(8-37) (AC187), an amylin receptor antagonist, blocks A-induced neurotoxicity. Treatment of cultures with AC187 before exposure to A results in significantly improved neuronal survival as judged by MTT and live-dead cell assays. Quantitative measures of A-evoked apoptotic cell death, using Hoechst and phosphotidylserine staining, confirm neuroprotective effects of AC187. We also demonstrate that AC187 attenuates the activation of initiator and effector caspases that mediate A-induced apoptotic cell death. These data are the first to show that expression of A toxicity may occur through the amylin receptor and suggest a novel therapeutic target for the treatment of AD.

Key words: AC187; Alzheimer's disease; diagonal band of Broca; neurodegeneration; apoptosis; caspase

---

Received March 22, 2004; revised May 3, 2004; accepted May 4, 2004.

This article has been cited by other articles:

				L. Saavedra, A. Mohamed, V. Ma, S. Kar, and E. P. de Chaves Internalization of -Amyloid Peptide by Primary Neurons in the Absence of Apolipoprotein E J. Biol. Chem., December 7, 2007; 282(49): 35722 - 35732. [Abstract] [Full Text] [PDF]

				G. J. Jones, N. L. Barsby, E. A. Cohen, J. Holden, K. Harris, P. Dickie, J. Jhamandas, and C. Power HIV-1 Vpr Causes Neuronal Apoptosis and In Vivo Neurodegeneration J. Neurosci., April 4, 2007; 27(14): 3703 - 3711. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help