Molecular basis for non-invasive diagnostics of cardiac amyloids using bone tracers DOI Creative Commons
Emily Lewkowicz,

Shobini Jayaraman,

Olga Gursky

et al.

Biomaterials Science, Journal Year: 2024, Volume and Issue: 12(17), P. 4275 - 4282

Published: Jan. 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.

Language: Английский

Alendronate and polyelectrolyte synergically induce biomimetic mineralization of collagen and demineralized dentin DOI
Leiqing Zhang, Zihuai Zhou, Shuo Zhang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142402 - 142402

Published: March 1, 2025

Language: Английский

Citations

0
Molecular basis for non-invasive diagnostics of cardiac amyloids using bone tracers DOI Creative Commons
Emily Lewkowicz,

Shobini Jayaraman,

Olga Gursky

et al.

Biomaterials Science, Journal Year: 2024, Volume and Issue: 12(17), P. 4275 - 4282

Published: Jan. 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.

Language: Английский

Citations

3