Approaches Based on Cholinergic Hypothesis and Cholinesterase Inhibitors in the Treatment of Alzheimer's Disease
Pp. 154-190 (37)
Zeynep Ozdemir, Azime-Berna Ozcelik and Mehtap Uysal
Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative
disease which deteriorates a person's ability to perform daily activities, leading to
various neuropsychiatric symptoms and behavioral disorders in later stages of the
disease. The pathophysiology of AD is complex. Biochemical studies indicate that
some neuromediator levels, especially acetylcholine, are reduced in the brain cortex.
Loss of neurons and axons associated with the onset of the disease causes lower levels
of acetylcholine release and it is more difficult to maintain the continuity of nerve
conduction in low concentration neurotransmitter levels. This has led to the
introduction of a “cholinergic hypothesis” that emphasizes the importance of
acetylcholine deficiency in the development of the symptoms of the disease. As the
(AChE) and (BChE) enzymes from the serine hydrolases which perform the hydrolysis
process of acetylcholine (ACh), the inhibition of these enzymes is an important method
of raising the level of acetylcholine. Studies indicate that increases in acetylcholine
levels due to acetylcholine esterase inhibition may improve cognitive impairment in the
early stages of AD.
AChE Inhibitors, Acetylcholine, Alzheimer’s Disease, BChE
Inhibitors, Cholinergic Hypothesis, Donepezile, Galantamine, Huperzin A,
Metrifonate, Physostigmine, Rivastigmine, Tacrine.
Inonu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Malatya, Turkey.