Contemporary Anticholinesterase Pharmaceuticals of Natural Origin and Their Synthetic Analogues for the Treatment of Alzheimers Disease

Abstract

Alzheimer's disease (AD), the most common form of dementia, is a degenerative and progressive neurological disorder characterized by deficit in the cholinergic transmission and formation of senile plaques containing beta-amyloid protein in the brain. Although complete pathology of the disease has not been fully elucidated yet, there are several treatment strategies for AD treatment. The complexity of AD is also due to involvement of several enzymes through its progression. Therefore, the most important therapeutic approach has emerged as inhibition of acetylcholinesterase (AChE), which is the key enzyme in the breakdown of acetylcholine. Another very attractive approach to lower beta-amyloid protein in fibrillar form has been the alpha- and beta-secretase inhibitors. On the other hand, recently, N-methyl-D-aspartate (NMDA) receptor antagonists have become a strong alternative, which has been approved to be effective in treatment of moderate to severe type of AD. Within the past few years, some pharmaceuticals have become available for clinical use; however, none of them have been shown to possess ability to discontinue the disease up to date. Hence, there is obviously a great need for discovery of new drug candidates of natural or synthetic origins for AD treatment. This review will cover AChE-inhibiting pharmaceuticals from plants and their synthetic derivatives including relevant patent literatures which may promise a future hope for AD treatment.

Evaluation of possible in vitro neurobiological effects of two varieties of Cupressus sempervirens (Mediterranean cypress) through their antioxidant and enzyme inhibition actions

“…AD is characterized by cognitive dysfunction, abnormalities in thinking and behaviors. Since the cholinergic deficit has been described in the brains of AD patients, cholinesterase inhibitors have become a foremost drug class for prescription of AD treatment [1]. As mammalian brain contains two major forms of cholinesterases; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), it is important to inhibit with both enzyme types.…”

Dietary polyunsaturated fatty acids improve cholinergic transmission in the aged brain

“…AChE inhibitors have, thus, far proven most efficacious in improving cognitive performance in the Alzheimer's disease patients and include both synthetic AChE inhibitors (tacrine and donepezil) and natural compounds [5,6]. In fact, one of the most widely used treatments for AD is the drug galantamine, originally isolated from the Galanthus worownii plant [7].…”

Acetylcholinesterase inhibition by medicinal plants: A Review

“…Several reviews on the newly discovered AChE inhibitors obtained from plants, fungus and marine organisms have also been published over the last years [12][13][14][15]. The majority of these AChE inhibitors belong to the alkaloid group, including indole, isoquinoline, quinolizidine, piperidine and steroidal alkaloids.…”