Degradation of Amyloid-β Species by Multi-Copper Oxidases
- Jing Yang 1,2, Kathleen Ran 1, Wenzhe Ma 3, Yanshi Chen 1, Yanxin Chen 1, Can Zhang 4, Hui Ye 5, Ying Lu 3, Chongzhao Ran 1
- Jing Yang 1,2, Kathleen Ran 1, Wenzhe Ma 3
- 1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Boston, MA, USA.
- 2School of Engineering, China Pharmaceutical University, Nanjing, China.
- 3Department of System Biology, Harvard Medical School, Boston, MA, USA.
- 4Department of Neurology, Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
- 5Department of Biology, Loyola University Chicago, IL, USA.
- 0Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Boston, MA, USA.
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View abstract on PubMed
Summary
This summary is machine-generated.Multi-copper oxidases (MCOs) can degrade amyloid-beta (Aβ) peptides, offering a new therapeutic strategy for Alzheimer's disease (AD). Ascorbate oxidase (AO) showed significant potential in rescuing neuron toxicity and preventing synaptic deficits.
Area Of Science
- Biochemistry
- Neuroscience
- Enzymology
Background
- Alzheimer's disease (AD) therapeutics often focus on reducing amyloid-beta (Aβ) production.
- Aβ degradation remains an underexplored therapeutic avenue for AD.
- Multi-copper oxidases (MCOs) are enzymes with potential but uninvestigated roles in Aβ clearance.
Purpose Of The Study
- To investigate the Aβ-degrading potential of MCOs.
- To evaluate MCOs as a novel therapeutic strategy for Alzheimer's disease.
Main Methods
- Assessed MCOs' Aβ degradation using electrophoresis.
- Validated ceruloplasmin (CP)-Aβ interactions via advanced microscopy and spectroscopy.
- Evaluated ascorbate oxidase (AO) in induced pluripotent stem (iPS) neuron cells and ex vivo brain slices.
Main Results
- CP and other MCOs demonstrated Aβ degradation capabilities.
- AO exhibited the most potent Aβ degradation among tested MCOs.
- AO treatment rescued Aβ oligomer-induced neurotoxicity and prevented hippocampal synaptic transmission deficits.
Conclusions
- This study is the first to report MCOs' peptide/protein degrading function.
- MCOs, particularly AO, show promise for Alzheimer's disease treatment.
- Further research into MCOs for AD therapy is warranted.
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