Background: Alzheimer's disease (AD) is an unexplained progressive degenerative brain
disease; it accounts for 60-70% of dementia cases worldwide, has an estimated global incidence of
24.3 million, and is associated with deterioration of the central nervous system. Acetylcholinesterase
(AChE) is an enzyme that catalyzes the breakdown of acetylcholine to acetate and choline. It is also
the potential target of most of the clinically used drugs for the treatment of AD. The degeneration of
cholinergic neurons and the loss of neural transmission are the main reasons for the decline of cognitive
ability in AD patients.
Objective: In recent years, the development of targeted drugs in AD has made significant achievements.
The global impact of AD continues to grow, and as a result, the focus of disease-modifying
therapies remains elusive. The role of treatment is not limited to pharmacology but involves many
factors, such as the psychological, social, and economic aspects of the patient and family. AChE is an
important target in AD to consider the use of AChE inhibitors in patients with mild to moderate AD,
even though the costs are high and no other direct progress has been made. Although there are many
AChE inhibitors, there is no selective potent inhibitor for AChE. There is still a need to address human
AChE structure, provide key insights into key protein-ligand interactions, and provide the basis
for molecular modeling and structure-based drug design.
Conclusion: In this review, we briefly introduce the clinical characteristics of AD, the development
of crystal structure, and the latest research on AD. In recent years, the development of different strategies
for amyloid-β, BACE1, and type-1 interferon receptor alpha-1 has attracted great attention.
There is an urgent need to further characterize available instrumental compounds to explore the use
of new selectivity and key protein-ligand interactions in AD. In the past few decades, great progress
has been made in the treatment of AD, but AD is still one of the world's problems, and the inability
to cure AD, indicates that there is an urgent need for new treatments.