The Inhibition of Acetylcholinesterase by Cone Snails Venom Peptides and their use in the Treatment of Alzheimer’s disease
Disciplines
Biochemistry | Bioinformatics | Computational Chemistry | Computational Neuroscience | Medicinal-Pharmaceutical Chemistry | Molecular and Cellular Neuroscience
Abstract (300 words maximum)
Alzheimer’s Disease (AD) is one of the costliest diseases for the American people, both in terms of the money spent and human suffering that it creates. Americans spent over 300 billion dollars in treating over 5 million patients with AD in 2020 alone. AD is a neurodegenerative disease that produces tangles and plaques within the brain, diminishing cognitive functioning and memory in those who are afflicted with the disease. These tangles and plaques disrupt the normal firing of neurons and lead to the eventual death and decay of parts of the brain. While there is currently no known cure, there are some drugs on the market that can help to lessen symptoms in mild to moderate forms of the disease. These drugs work by inhibiting Acetylcholinesterase (AChE), a protein within the brain that breaks down the neurotransmitter acetylcholine (ACh). Patients with AD have a deficient amount of ACh within their brain, and these drugs work to increase the amount of ACh. Nonetheless, there are limitations to these drugs, including their limited efficacy and side effects. The venom of the cone snail may provide an exciting alternative to the drugs that currently exist. Cone snails use these toxins not only for hunting, but also for self-defense from larger animals. The goal of this research project is to identify the best venom peptides inhibiting the AChE. In this study, we screened over 70 different kinds of peptides for their ability to inhibit AChE. Various bioinformatics tools such as PATCHDOCK and FIREDOCK were used to identify the strength of peptides inhibiting the AChE. We found several high efficacy peptides including BP0361 and BP0362. BP0362 showed a binding affinity of -84.54 kcal/mol whereas BP0361 exhibited the binding affinity of -85.17 kcal/mol. We plan to synthesize these peptides and test their in-vitro efficiency.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
The Inhibition of Acetylcholinesterase by Cone Snails Venom Peptides and their use in the Treatment of Alzheimer’s disease
Alzheimer’s Disease (AD) is one of the costliest diseases for the American people, both in terms of the money spent and human suffering that it creates. Americans spent over 300 billion dollars in treating over 5 million patients with AD in 2020 alone. AD is a neurodegenerative disease that produces tangles and plaques within the brain, diminishing cognitive functioning and memory in those who are afflicted with the disease. These tangles and plaques disrupt the normal firing of neurons and lead to the eventual death and decay of parts of the brain. While there is currently no known cure, there are some drugs on the market that can help to lessen symptoms in mild to moderate forms of the disease. These drugs work by inhibiting Acetylcholinesterase (AChE), a protein within the brain that breaks down the neurotransmitter acetylcholine (ACh). Patients with AD have a deficient amount of ACh within their brain, and these drugs work to increase the amount of ACh. Nonetheless, there are limitations to these drugs, including their limited efficacy and side effects. The venom of the cone snail may provide an exciting alternative to the drugs that currently exist. Cone snails use these toxins not only for hunting, but also for self-defense from larger animals. The goal of this research project is to identify the best venom peptides inhibiting the AChE. In this study, we screened over 70 different kinds of peptides for their ability to inhibit AChE. Various bioinformatics tools such as PATCHDOCK and FIREDOCK were used to identify the strength of peptides inhibiting the AChE. We found several high efficacy peptides including BP0361 and BP0362. BP0362 showed a binding affinity of -84.54 kcal/mol whereas BP0361 exhibited the binding affinity of -85.17 kcal/mol. We plan to synthesize these peptides and test their in-vitro efficiency.