| Summary: | Alzheimer's disease (AD) affects millions of people around the world and currently there are no effective therapies. Cotinine, a metabolite of nicotine, has been shown to be neuroprotective, prevent memory loss and reduce amyloid-β (Aβ) plaque pathology in transgenic AD mice. The beneficial effect that cotinine has on memory is associated with the inhibition of Aβ aggregation, the stimulation of pro-survival factors such as Akt, and the inhibition of pro-apoptotic factors such as glycogen synthase kinase 3 beta (GSK3β). These pro-apoptotic factors promote neuronal survival and the synaptic plasticity processes underlying learning and memory in the hippocampus and cortex of wild type and AD mice. Cotinine has also shown to diminish depressive-like behavior in normal and chronically stressed mice. Additionally, the use of this compound in studies has resulted in an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices. It can be observed in multiple studies, that daily treatment of mice with cotinine reduced Aβ levels and plaque formation compared with vehicle treated mice, which had higher memory loss and depressive behavior. The beneficial effects of cotinine on brain function and good safety profile, suggest that it may be a potential new therapeutic agent against Alzheimer's disease.
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