Title : Cotinine reduces amyloid-beta aggregation and improves memory in Alzheimer's disease mice - Echeverria_2011_J.Alzheimers.Dis_24_817 |
Author(s) : Echeverria V , Zeitlin R , Burgess S , Patel S , Barman A , Thakur G , Mamcarz M , Wang L , Sattelle DB , Kirschner DA , Mori T , Leblanc RM , Prabhakar R , Arendash GW |
Ref : J Alzheimers Dis , 24 :817 , 2011 |
Abstract :
Alzheimer's disease (AD) affects millions of people world-wide and new effective and safe therapies are needed. Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans. We studied the effect of cotinine on amyloid-beta (Abeta) aggregation as well as addressed its impact on working and reference memories. Cotinine reduced Abeta deposition, improved working and reference memories, and inhibited Abeta oligomerization in the brains of transgenic (Tg) 6799 AD mice. In vitro studies confirmed the inhibitory effect of cotinine on Abeta1-42 aggregation. Cotinine stimulated Akt signaling, including the inhibition of glycogen synthase kinase 3beta (GSK3beta), which promotes neuronal survival and the synaptic plasticity processes underlying learning and memory in the hippocampus and cortex of wild type and Tg6799 AD mice. Simulation of the cotinine-Abeta1-42 complex using molecular dynamics showed that cotinine may interact with key histidine residues of Abeta1-42, altering its structure and inhibiting its aggregation. The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of AD. |
PubMedSearch : Echeverria_2011_J.Alzheimers.Dis_24_817 |
PubMedID: 21321389 |
Inhibitor | Cotinine |
Echeverria V, Zeitlin R, Burgess S, Patel S, Barman A, Thakur G, Mamcarz M, Wang L, Sattelle DB, Kirschner DA, Mori T, Leblanc RM, Prabhakar R, Arendash GW (2011)
Cotinine reduces amyloid-beta aggregation and improves memory in Alzheimer's disease mice
J Alzheimers Dis
24 :817
Echeverria V, Zeitlin R, Burgess S, Patel S, Barman A, Thakur G, Mamcarz M, Wang L, Sattelle DB, Kirschner DA, Mori T, Leblanc RM, Prabhakar R, Arendash GW (2011)
J Alzheimers Dis
24 :817