the effect of copper chelators on zn(-) superoxide dismutase
DESCRIPTION
The effect of copper chelators on Zn(-) Superoxide Dismutase. Lucy Brennan Dr. Joe Beckman Dr. Kari Trumbull. Amyotrophic Lateral Sclerosis. Motor neuron disease characterized by progressive paralysis 10% of cases are familial Mutations in SOD account for up to 7% of fALS. - PowerPoint PPT PresentationTRANSCRIPT
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The effect of copper chelators on Zn(-) Superoxide DismutaseThe effect of copper chelators on Zn(-) Superoxide Dismutase
Lucy Brennan
Dr. Joe Beckman
Dr. Kari Trumbull
Lucy Brennan
Dr. Joe Beckman
Dr. Kari Trumbull
![Page 2: The effect of copper chelators on Zn(-) Superoxide Dismutase](https://reader036.vdocuments.us/reader036/viewer/2022062305/568157c2550346895dc54495/html5/thumbnails/2.jpg)
Amyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis
Motor neuron disease characterized by progressive paralysis
10% of cases are familial Mutations in SOD account for up to 7% of
fALS
Motor neuron disease characterized by progressive paralysis
10% of cases are familial Mutations in SOD account for up to 7% of
fALS
![Page 3: The effect of copper chelators on Zn(-) Superoxide Dismutase](https://reader036.vdocuments.us/reader036/viewer/2022062305/568157c2550346895dc54495/html5/thumbnails/3.jpg)
Superoxide dismutaseSuperoxide dismutase
(Cu2+ Zn)SOD+O2---> (Cu1+ Zn)SOD+O2
(Cu1+ Zn)SOD +O2-+2H+--> (Cu2+ Zn)SOD+H2O2
Mutations linked to structural instability Zn(-)SOD has a toxic gain of function believed to
underlie fALS (Cu1+)SOD +O2--> (Cu2+)SOD+ 02
-
(Cu2+ Zn)SOD+O2---> (Cu1+ Zn)SOD+O2
(Cu1+ Zn)SOD +O2-+2H+--> (Cu2+ Zn)SOD+H2O2
Mutations linked to structural instability Zn(-)SOD has a toxic gain of function believed to
underlie fALS (Cu1+)SOD +O2--> (Cu2+)SOD+ 02
-
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Copper chelatorsCopper chelators
Dimercaptrol (BAL)
treatment for heavy metal toxicity and Wilson’s disease
Sulfhydral complex
Dimercaptrol (BAL)
treatment for heavy metal toxicity and Wilson’s disease
Sulfhydral complex
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GoalsGoals
Validation of WST assay To find a Cu-chelator that effectively
removes copper from SOD Modifying the Cu-chelator into a
potential drug for ALS
Validation of WST assay To find a Cu-chelator that effectively
removes copper from SOD Modifying the Cu-chelator into a
potential drug for ALS
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WST assayWST assay
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Superoxide detectionSuperoxide detection
An assay including potassium superoxide and WST-1 was performed
Addition of KO2- was
added to the assay WST has been
reduced
An assay including potassium superoxide and WST-1 was performed
Addition of KO2- was
added to the assay WST has been
reduced
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Xanthine assayXanthine assay
WST-1 + Xanthine and Xanthine oxidase An increased
absorbance was noted, indicating that WST-1 is reacting with superoxide
WST-1 + Xanthine and Xanthine oxidase An increased
absorbance was noted, indicating that WST-1 is reacting with superoxide
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Addition of BAL with Zn(-)SODAddition of BAL with Zn(-)SOD
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ImplicationsImplications
Validation of WST assay Limitations
Insight into activity of Zn(-)SOD Possible chelation therapy for ALS
Viable test for such compounds
Validation of WST assay Limitations
Insight into activity of Zn(-)SOD Possible chelation therapy for ALS
Viable test for such compounds
![Page 11: The effect of copper chelators on Zn(-) Superoxide Dismutase](https://reader036.vdocuments.us/reader036/viewer/2022062305/568157c2550346895dc54495/html5/thumbnails/11.jpg)
AcknowledgementsAcknowledgements
HHMI Kevin Ahern Dr. Joe Beckman Dr. Kari Trumbull
HHMI Kevin Ahern Dr. Joe Beckman Dr. Kari Trumbull