AI Article Synopsis
- The study investigates catalytic photo-oxygenation as a potential therapy for tauopathies like Alzheimer’s disease, focusing on the complex structure of tau proteins.
- Researchers developed two assay systems to quantitatively analyze the catalytic activity on tau from human patients, emphasizing the oxygenation of histidine residues.
- Findings indicate a promising catalyst for oxygenating human tau but reveal differences between heparin-induced aggregated tau and tau from actual Alzheimer’s patients, which may impact the effectiveness of photo-oxygenation strategies.
Article Abstract
Catalytic photo-oxygenation of tau amyloid is a potential therapeutic approach to tauopathies, including Alzheimer disease (AD). However, tau is a complex target containing great molecular size and heterogeneous isoforms/proteoforms. Although catalytic photo-oxygenation has been confirmed when using catalyst and recombinant tau pretreated with heparin, its effects on tau from human patients have not yet been clarified. In this study, focusing on the histidine residues being oxygenated, we have constructed two assay systems capable of quantitatively evaluating the catalytic activity when used on human patient tau: (1) fluorescence labeling at oxygenated histidine sites and (2) LC-MS/MS analysis of histidine-containing fragments. Using these assays, we identified as a promising catalyst for oxygenation of human tau. In addition, our results suggest that aggregated tau induced by heparin is different from actual AD patient tau in developing effective photo-oxygenation catalysts.
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| http://dx.doi.org/10.1021/acschemneuro.3c00264 | DOI Listing |
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