Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer's Disease

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 beta-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.

Automated summary

Alzheimer's disease is a common cause of dementia in the elderly population, but there is no effective treatment currently available. The increasing life expectancy worldwide is expected to lead to a significant rise in Alzheimer's disease rates, necessitating the urgent search for new drugs. Alkaloids, particularly harmine and isoquinoline alkaloids, show promise as multi-target compounds for Alzheimer's disease by inhibiting key enzymes involved in its pathophysiology. However, further research is needed to explore their mechanisms of action and develop potentially better synthetic analogues.