Natural products and their derivatives as cholinesterase inhibitors in the treatment of neurodegenerative disorders: an update

Alzheimer’s disease (AD) is the most common form of neurodegenerative disorders. If more effective therapies than the onescurrently available are not developed that either prevent AD or other neurodegenerative or block progression of the diseases in its veryearly stages, the economic and societal cost of caring for AD patients will be devastating. Besides the neuropathologic hallmarks of thediseases, namely neurofibrillary tangles and AD neuritic plaques, the disease is characterized neurochemically by a consistent deficit incholinergic neurotransmission, particularly affecting cholinergic neurons in basal forebrain. AD and other forms of dementia could betreated by the use of agents which restore the level of acetylcholine through inhibition of both two major forms of cholinesterase: acetylcholinesterase(AChE) and butyrylcholinesterase (BChE). Moreover, the inhibition of AChE holds a key role not only to enhance cholinergictransmission in the brain but also to reduce the aggregation of amyloid and the formation of the neurotoxic fibrils in AD. Followingthis view, in recent years, an increased interest has emerged directed to finding drugs able to inhibit both of these events. This reviewsummarizes and highlights recent advances in current knowdlege on natural products as cholinesterase inhibitors and how thesecompounds have also served as the starting points for semi-synthetic analogs with improved properties.