Project Title

Scorpion Venom Peptides to Inhibit Acetylcholinesterase for Alzheimer’s Disease

Academic department under which the project should be listed

CSM - Chemistry and Biochemistry

Faculty Sponsor Name

Mohammad A. Halim

Abstract (300 words maximum)

Alzheimer’s Disease (AD) is a continuous neurodegenerative disorder marked by a decline in cognition and memory. Within the United States, there are currently an estimated 6.2 million adults aged 65 and older suffering from the disease. If the disease continues at its current rate, an estimated 13.8 million adults will suffer by 2060. The most recent data shows that 121,499 deaths occurred with AD being the cause in 2019, making it the sixth-leading cause of death within the United States. Whereas other diseases that are the leading causes of death in the United States have been on a gradual decline, AD related deaths increased more than 145% from 2000 to 2019. Acetylcholine (ACh) is a prominent neurotransmitter in the brain and plays a key role in human cognition, forming memories, and our ability to concentrate. Those who present with AD have been shown to have a deficit in acetylcholine (ACh). Most medications currently prescribed for AD inhibit Acetylcholinesterase (AChE), the enzyme which breaks down acetylcholine after it has sent the signal from the brain. It has been shown that these inhibitor drugs of Acetylcholinesterase (AChE) can increase the acetylcholine (ACh) level and sustain the duration of neurotransmitter action. Although these medications seek to lessen the cognitive deficit associated with AD, they are only effective in treating mild to moderate AD. In addition to this, they present with restricted efficacy, limited bioavailability, and adverse cholinergic side effects. Various studies disclosed that venom toxin can be used to treat neurodegenerative diseases. In this study, we have screened 18 scorpion venom peptides inhibiting the AChE. Various computational tools such as PEP-FOLD, PATCHDOCK and FIREDOCK were used to identify the potent peptides against AChE. The top four peptides had binding affinities greater than -80 kcal/mol. The remaining peptides had affinities in the range from -70 kcal/mol to 79 kcal/mol. Among these peptides, AVP2058 showed the highest binding affinity. This peptide also interacts with the important residues such as Trp279, Arg289 and His440 of AChE. These results showed that venom peptides can effectively bind to the active sites of AChE and can act as potential candidates for the future treatment of Alzheimer’s disease.

Disciplines

Biochemistry | Bioinformatics | Computational Chemistry | Computational Neuroscience | Medicinal-Pharmaceutical Chemistry | Molecular and Cellular Neuroscience

Project Type

Poster

How will this be presented?

Yes, in person

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Scorpion Venom Peptides to Inhibit Acetylcholinesterase for Alzheimer’s Disease

Alzheimer’s Disease (AD) is a continuous neurodegenerative disorder marked by a decline in cognition and memory. Within the United States, there are currently an estimated 6.2 million adults aged 65 and older suffering from the disease. If the disease continues at its current rate, an estimated 13.8 million adults will suffer by 2060. The most recent data shows that 121,499 deaths occurred with AD being the cause in 2019, making it the sixth-leading cause of death within the United States. Whereas other diseases that are the leading causes of death in the United States have been on a gradual decline, AD related deaths increased more than 145% from 2000 to 2019. Acetylcholine (ACh) is a prominent neurotransmitter in the brain and plays a key role in human cognition, forming memories, and our ability to concentrate. Those who present with AD have been shown to have a deficit in acetylcholine (ACh). Most medications currently prescribed for AD inhibit Acetylcholinesterase (AChE), the enzyme which breaks down acetylcholine after it has sent the signal from the brain. It has been shown that these inhibitor drugs of Acetylcholinesterase (AChE) can increase the acetylcholine (ACh) level and sustain the duration of neurotransmitter action. Although these medications seek to lessen the cognitive deficit associated with AD, they are only effective in treating mild to moderate AD. In addition to this, they present with restricted efficacy, limited bioavailability, and adverse cholinergic side effects. Various studies disclosed that venom toxin can be used to treat neurodegenerative diseases. In this study, we have screened 18 scorpion venom peptides inhibiting the AChE. Various computational tools such as PEP-FOLD, PATCHDOCK and FIREDOCK were used to identify the potent peptides against AChE. The top four peptides had binding affinities greater than -80 kcal/mol. The remaining peptides had affinities in the range from -70 kcal/mol to 79 kcal/mol. Among these peptides, AVP2058 showed the highest binding affinity. This peptide also interacts with the important residues such as Trp279, Arg289 and His440 of AChE. These results showed that venom peptides can effectively bind to the active sites of AChE and can act as potential candidates for the future treatment of Alzheimer’s disease.

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