Enzyme Inhibitors Involved in the Treatment of Alzheimer’s Disease
Pp. 142-198 (57)
Vageesh Revadigar, Raza Murad Ghalib, Vikneswaran Murugaiyah, Mohamed A. Embaby, Ali Jawad, Sayed Hasan Mehdi, Rokiah Hashim and Othman Sulaiman
Alzheimer disease (AD), a chronic and progressive neurodegenerative
disease is the leading cause of dementia among older people. Several hypotheses exist
on the pathogenesis of AD. According to the cholinergic hypothesis, there is an
irreversible deficiency in cholinergic functions of brain resulting in substantial reduction
of the neurotransmitter, acetylcholine. In contrast, amyloid hypothesis suggests that
amyloid beta (Aβ) deposits are fundamental cause of the neurodegeneration. There is
also an involvement of another protein, tau protein, which twists into abnormal tangles
and lead to the death of brain cells. This chapter aims to provide a comprehensive
review on the various enzymes involved in the pathogenic cascade of AD and their
potential inhibitors. The chapter starts with a general overview on the enzymes,
outlining their morphological and functional features and how they are involved in the
pathogenesis of AD. The following section addresses the enzymes inhibitors at various
stages of drug development, highlighting their mechanisms of action, advantages,
limitations and potential clinical applications.
Alzheimer’s disease, acetycholinesterase, amyloid precursor protein,
α-secretase, αβ-peptide, begacestat (GSI-953), bisnorcymserine, BMS-708163, β-
secretase, butyrylcholinesterase, CTS-21166, donepezil, ELND006, galantamine,
huperzine A, LY2811376, PF-3084014, (-)-Phenserine, rivastigmine, semagacestat
(LY-450139), senile plaques, γ-secretase.
Department of Chemistry, Faculty of Sciences & Arts Khulais, King Abdulaziz University, Jeddah, KSA.