Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease
The leading hypothesis for Alzheimer's Disease (AD) has traditionally focused on the aggregation of Amyloid-β into amyloid plaques. However, research has yet to definitively prove the role of the amyloid peptide in the pathology of the disease. Given that all therapeutics targeting amyloid plaq...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Brain Disorders |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666459323000136 |
| _version_ | 1797825574605946880 |
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| author | Arnulfo Pulido Benjamin Hulbert Hayleigh Giese Sabrina Kurian Rebbeca Rozhon Michael Zambrano Oscar Diaz Mariam Abd Madison Caputo Daniel S. Kissel Mallory A. Havens |
| author_facet | Arnulfo Pulido Benjamin Hulbert Hayleigh Giese Sabrina Kurian Rebbeca Rozhon Michael Zambrano Oscar Diaz Mariam Abd Madison Caputo Daniel S. Kissel Mallory A. Havens |
| author_sort | Arnulfo Pulido |
| collection | DOAJ |
| description | The leading hypothesis for Alzheimer's Disease (AD) has traditionally focused on the aggregation of Amyloid-β into amyloid plaques. However, research has yet to definitively prove the role of the amyloid peptide in the pathology of the disease. Given that all therapeutics targeting amyloid plaques have failed in clinical trials, with one exception, there is a need to explore alternative approaches to treatment of this disease. Therefore, we examined other factors that are altered during AD pathogenesis. Many AD patients have dysregulation of metal ions, such as copper and zinc, in addition to accumulation of Amyloid-β. The interaction between Amyloid-β and copper can result in the production of reactive oxygen species (ROS). ROS can cause damage to neurons and surrounding tissues resulting in degradation of the brain. Therefore, our work focuses on disrupting the interaction between Amyloid-β and copper via chelation therapy to prevent ROS formation and, in turn, reduce neurotoxicity. In this study, copper chelation with beta alanine reduced the amount of ROS produced in the brains of C. elegans expressing pan-neuronal Amyloid-β, amino acids 1-42. In response to chelation, the expression of the antioxidant gene, gst-4, was also reduced. Importantly, there was also a positive correlation between copper chelation and increased lifespan in the Amyloid-β expressing C. elegans. Consistent with our previous in vitro work, Amyloid-β expression in vivo was not altered following treatment. Taken together, these results suggest that copper chelation has the potential to serve as an AD therapeutic resulting in increased longevity. |
| first_indexed | 2024-03-13T10:55:57Z |
| format | Article |
| id | doaj.art-0d03d35100fb49cf890047d6797d84ef |
| institution | Directory Open Access Journal |
| issn | 2666-4593 |
| language | English |
| last_indexed | 2024-03-13T10:55:57Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Disorders |
| spelling | doaj.art-0d03d35100fb49cf890047d6797d84ef2023-05-17T04:23:33ZengElsevierBrain Disorders2666-45932023-06-0110100076Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's DiseaseArnulfo Pulido0Benjamin Hulbert1Hayleigh Giese2Sabrina Kurian3Rebbeca Rozhon4Michael Zambrano5Oscar Diaz6Mariam Abd7Madison Caputo8Daniel S. Kissel9Mallory A. Havens10Department of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Chemistry, 1 University Parkway Lewis University, Romeoville, IL 60446 USADepartment of Biology, 1 University Parkway Lewis University, Romeoville, IL 60446 USA; Corresponding author.The leading hypothesis for Alzheimer's Disease (AD) has traditionally focused on the aggregation of Amyloid-β into amyloid plaques. However, research has yet to definitively prove the role of the amyloid peptide in the pathology of the disease. Given that all therapeutics targeting amyloid plaques have failed in clinical trials, with one exception, there is a need to explore alternative approaches to treatment of this disease. Therefore, we examined other factors that are altered during AD pathogenesis. Many AD patients have dysregulation of metal ions, such as copper and zinc, in addition to accumulation of Amyloid-β. The interaction between Amyloid-β and copper can result in the production of reactive oxygen species (ROS). ROS can cause damage to neurons and surrounding tissues resulting in degradation of the brain. Therefore, our work focuses on disrupting the interaction between Amyloid-β and copper via chelation therapy to prevent ROS formation and, in turn, reduce neurotoxicity. In this study, copper chelation with beta alanine reduced the amount of ROS produced in the brains of C. elegans expressing pan-neuronal Amyloid-β, amino acids 1-42. In response to chelation, the expression of the antioxidant gene, gst-4, was also reduced. Importantly, there was also a positive correlation between copper chelation and increased lifespan in the Amyloid-β expressing C. elegans. Consistent with our previous in vitro work, Amyloid-β expression in vivo was not altered following treatment. Taken together, these results suggest that copper chelation has the potential to serve as an AD therapeutic resulting in increased longevity.http://www.sciencedirect.com/science/article/pii/S2666459323000136Alzheimer's diseaseChelation therapyReactive oxygen speciesC. elegans |
| spellingShingle | Arnulfo Pulido Benjamin Hulbert Hayleigh Giese Sabrina Kurian Rebbeca Rozhon Michael Zambrano Oscar Diaz Mariam Abd Madison Caputo Daniel S. Kissel Mallory A. Havens Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease Brain Disorders Alzheimer's disease Chelation therapy Reactive oxygen species C. elegans |
| title | Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease |
| title_full | Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease |
| title_fullStr | Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease |
| title_full_unstemmed | Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease |
| title_short | Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease |
| title_sort | copper chelation via beta alanine extends lifespan in a c elegans model of alzheimer s disease |
| topic | Alzheimer's disease Chelation therapy Reactive oxygen species C. elegans |
| url | http://www.sciencedirect.com/science/article/pii/S2666459323000136 |
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