Title:Modulators of Acetylcholinesterase Activity: From Alzheimer's Disease to Anti-Cancer Drugs
VOLUME: 24 ISSUE: 30
Author(s):Tamara Lazarevic-Pasti *, Andreja Leskovac, Tatjana Momic, Sandra Petrovic and Vesna Vasic*
Affiliation:Department of Physical Chemistry, Vinca Institute of Nuclear Sciences, University of Belgrade, M. Petrovica Alasa 12-14, 11001 Belgrade, Department of Physical Chemistry, Vinca Institute of Nuclear Sciences, University of Belgrade, M. Petrovica Alasa 12-14, 11001 Belgrade, Department of Physical Chemistry, Vinca Institute of Nuclear Sciences, University of Belgrade, M. Petrovica Alasa 12-14, 11001 Belgrade, Department of Physical Chemistry, Vinca Institute of Nuclear Sciences, University of Belgrade, M. Petrovica Alasa 12-14, 11001 Belgrade, Department of Physical Chemistry, Vinca Institute of Nuclear Sciences, University of Belgrade, M. Petrovica Alasa 12-14, 11001 Belgrade
Keywords:Acetylcholinesterase, Alzheimer's disease, Parkinson's disease, cancer treatment, drug design, apoptosis.
Abstract:Background: Acetylcholinesterase (AChE) is involved in the termination of
impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous
cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation
leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic
receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting
with the enzyme as their primary target, are applied as relevant drugs for different
neurodegenerative diseases (such as Alzheimer's and Parkinson's) as well as toxins. At the
same time, there are increasing evidence that in non-neuronal context, AChE is involved
in the regulation of cell proliferation, differentiation, apoptosis and cell-cell interaction.
An irregular expression of AChE has been found in different types of tumors, suggesting
the involvement of AChE in the regulation of tumor development. Having all this in
mind, there is a possibility that some AChE inhibitors could be used as anti-cancer agents.
Objective: This contribution will discuss a broad range of possible application of different
AChE inhibitors as drugs, from well-known anti-Alzheimer's disease drugs to their use in
cancer treatment in future. Emphasis will be put on various known AChE inhibitors
classes, whose application as drugs could be controversy, as well as on newly investigated
natural products, which can also modulate AChE activity.
Conclusion: It is not clear a patient treated for neurodegenerative condition prone to increased
risk for some types of cancer and vice versa. This is necessary to keep in mind
during rational drug design process for all therapies, which are based on AChE as a target
molecule.
