Alzheimer's disease (AD) is the most common cause of dementia in elderly people; currently, there is no efficient treatment. Considering the increase in life expectancy worldwide AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. A great amount of experimental and clinical evidence indicated that AD is a complex disorder characterized by widespread neurodegeneration of the CNS, with major involvement of the cholinergic system, causing progressive cognitive decline and dementia. The current treatment, based on the cholinergic hypothesis, is only symptomatic and mainly involves the restoration of acetylcholine (ACh) levels through the inhibition of acetylcholinesterase (AChE). Since the introduction of the Amaryllidaceae alkaloid galanthamine as an antidementia drug in 2001, alkaloids have been one of the most attractive groups for searching for new AD drugs. The present review aims to comprehensively summarize alkaloids of various origins as multi-target compounds for AD. From this point of view, the most promising compounds seem to be the β-carboline alkaloid harmine and several isoquinoline alkaloids since they can simultaneously inhibit several key enzymes of AD's pathophysiology. However, this topic remains open for further research on detailed mechanisms of action and the synthesis of potentially better semi-synthetic analogues.

School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth PO1 2DT UK

Secondary Metabolites of Plants as Potential Drugs Research Group Department of Pharmacognosy and Pharmaceutical Botany Faculty of Pharmacy Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

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