Ross Zeitlin
Tanzania
Research Article
Cotinine Inhibits Amyloid-ß Peptide Neurotoxicity and Oligomerization
Author(s): Sarah Burgess, Ross Zeitlin and Valentina EcheverriaSarah Burgess, Ross Zeitlin and Valentina Echeverria
Alzheimer’s disease, the main cause of dementia, correlates with an increase in the brain levels of aggregated forms of amyloid-β (Aβ) peptide. We investigated the effect of cotinine, the main metabolite of nicotine, on Aβ 1-42 neurotoxicity. Compared to nicotine, cotinine has a longer plasma half-life, lower toxicity and is a poor agonist of the nicotinic acetylcholine receptors (nAChRs). We found that cotinine promoted the survival of primary cortical neurons exposed to Aβ 1-42 . This neuroprotective effect was independent of the agonistic activation of the nAChRs and it was not prevented by the general nAChR antagonist mecamylamine. However, it was prevented by the pre-aggregation of Aβ in absence of cotinine, suggesting that inhibition of Aβ 1-42 aggregation by cotinine is a key mechanism mediating its neuroprotective activity. The analysis of A.. View More»
