Natural Products for Treatment of Alzheimer's Disease and Related Diseases: Understanding their Mechanism of Action

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with memory impairment and cognitive deficit, which is characterized with low levels of acetylcholine, a neurotransmitter, in the brain of the patients. Histopathological hallmarks of AD include deposition of -amyloid (A ) plaques and formation of neurofibrillary tangles. According to the cholinergic hypothesis, the acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylcholine and the inhibition of AChE improves the levels of acetylcholine in the brain, enhancing cholinergic functions in patients. AChE inhibitors (AChEi) can alleviate the symptoms of AD, even though they do not halt or reverse the disease progress. Currently, most of the drugs approved by the US-FDA for the treatment of AD are AChEi. For example, galanthamine is a natural alkaloid obtained from Galanthus spp. Huperzine A, an alkaloid found in Huperzia spp., is an AChEi commercialized as a dietary supplement for memory support, used to treat AD symptoms in China. Extent reports on pathology of AD have made it important to discovery regarding mechanism of disease and potential therapeutic targets. This issue focused on the medicinal chemistry aspects of new natural products used for treatment of AD including the mechanism, the molecular aspects, as well as the new strategy of using natural products for AD.