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Related Concept Videos

Cholinesterases: Distribution and Function01:22

Cholinesterases: Distribution and Function

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Cholinesterases are a group of serine hydrolase enzymes that play a crucial role in the breakdown of choline esters. The two primary types of cholinesterases are acetylcholinesterases (AChEs) and butyrylcholinesterase (BuChEs), which differ in their distribution, function, and substrate specificity. AChEs, also known as true cholinesterases, specifically hydrolyze acetylcholine, while BuChEs, often referred to as pseudocholinesterases, can hydrolyze various choline esters, including...
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Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.     
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Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
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Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
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Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
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Acetylcholinesterase and human cancers.

Stephen D Richbart1, Justin C Merritt1, Nicholas A Nolan2

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Advances in Cancer Research
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Summary

Acetylcholinesterase (AChE) regulates cancer progression and is altered in tumors. Existing AChE-modulators, used for neurodegenerative disorders, show potential for repurposing as novel cancer therapies.

Keywords:
AChE-modulatorsAcetylcholinesteraseAnti-cancer drugCancerExpressionIsoforms

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Acetylcholinesterase (AChE) is a serine hydrolase primarily degrading acetylcholine (ACh) to terminate neurotransmission.
  • Beyond neuronal function, AChE influences non-neuronal processes including cell growth, apoptosis, and inflammation.
  • Altered AChE activity in human tumors suggests a role in cancer pathophysiology.

Purpose of the Study:

  • To provide a comprehensive overview of the AChE-signaling pathway's contribution to human cancer growth and progression.
  • To explore the expression of AChE isoforms (AChE-T, AChE-R, AChE-S) in human cancers.
  • To discuss the potential repurposing of AChE-modulators for cancer treatment.

Main Methods:

  • Review of published literature on AChE function in cancer.
  • Analysis of AChE expression in human cancer cell lines and patient tumors.
  • Exploration of existing AChE-modulators for therapeutic potential.

Main Results:

  • AChE is a key regulator of oncogenic pathways, including proliferation, differentiation, adhesion, migration, invasion, and metastasis.
  • AChE isoforms are significantly expressed in human cancer cell lines and tumors.
  • Existing drugs targeting AChE for neurodegenerative diseases may be repurposed for cancer therapy.

Conclusions:

  • The AChE-signaling pathway plays a critical role in the progression of human cancers.
  • AChE isoforms are relevant targets in cancer treatment.
  • Repurposing AChE-modulators offers a promising avenue for novel cancer therapies, pending discovery of selective ligands.