Molecular basis for non-invasive diagnostics of cardiac amyloids using bone tracers

Biomaterials Science, Год журнала: 2024, Номер 12(17), С. 4275 - 4282

Опубликована: Янв. 1, 2024

Amyloid diseases including Alzheimer's, Parkinson's and over 30 others are incurable life-threatening disorders caused by abnormal protein deposition as fibrils in various organs. Cardiac amyloidosis is particularly challenging to diagnose treat. Identification of the fibril-forming protein, which heart usually amyloid transthyretin (ATTR) or immunoglobulin light chain (AL), paramount treatment. A transformative non-invasive diagnostic modality imaging using technetium-labeled pyrophosphate diphosphonate bone tracers, 99mTc-PYP/DPD/HMDP. For unknown reasons, these tracers show preferential uptake ATTR deposits. The tracer-binding moiety potentially involves and/or amyloid-associated calcific We propose that, like bone, chelate surface-bound Ca2+ amyloid. In high-affinity sites, coordinated pairs acidic residues. To identify such residues on amyloids, we harnessed atomic structures patient-derived cardiac amyloids determined cryogenic electron microscopy since 2019. These help explain why most but not all deposits 99mTc-PYP/DPD/HMDP radiotracers, while AL opposite true. Moreover, fibril greater microcalcification observed vs. findings may aid diagnostics therapeutic targeting relevant other amyloids.

Язык: Английский

Alendronate and polyelectrolyte synergically induce biomimetic mineralization of collagen and demineralized dentin

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 142402 - 142402

Опубликована: Март 1, 2025

Язык: Английский

Amyloid-induced mineralization: From biological systems to biomimetic materials

Bioactive Materials, Год журнала: 2025, Номер 51, С. 469 - 493

Опубликована: Май 21, 2025

Язык: Английский