Understanding the link between nicotinic receptors and amyloid toxicity in Alzheimer's disease

Research around nicotinic receptors has largely focused on cognition. Consequently nicotinic receptor ligands have been developed for various disorders associated with cognitive dysfunction such as schizophrenia, ADHD and Alzheimer's disease.

Involvement of nicotinic receptors in Alzheimer's disease particularly interesting as, in addition to improving cognition through direct effects on nerve pathways, a growing body of data have demonstrated the ability of α7 nicotinic agonists to reduce amyloid toxicity in the brain. Amyloid1-42 has been associated with the development of Alzheimer's.

Exactly how α7 nicotinic agonists impact on the effect of amyloid is unknown. Some believe that agonists prevent amyloid binding to, and excessively activating hippocampal cells. Another hypothesis can be postulated supported by data appearing in the February issue of Neurochemical research. This research suggests that activation of α4β2 nAChR by nicotine decreases BACE1 expression. BACE1 is responsible for the production of Aβ, and this was suggested by the authors to explain why levels are reduced in hippocampal neurons following nicotinic receptor stimulation.

The full paper can be accessed through http://www.leaddiscovery.co.uk/articles/21336821 - if you are involved in the development of nicotinic agents you may also be interested in LeadDiscovery's monthly service UpdatesPlus-Nicotinic receptors - http://www.leaddiscovery.co.uk/updatesplus

Further information about Alzheimer's disease for pharmaceutical personel:

Alzheimer's Disease: Current Treatment Practices and Opportunities, 2010