Effective and accessible treatments for Alzheimer's disease (AD) are urgently needed. Soluble Aβ oligomers are identified as neurotoxic species in AD and targeted in antibody-based drug development to mitigate cognitive decline. However, controversy exists concerning their efficacy and safety. In this study, an alternative strategy is proposed to inhibit the formation of Aβ oligomers by selectively oxidizing specific amino acids in the Aβ sequence, thereby preventing its aggregation. Targeted oxidation is achieved using biocompatible and blood-brain barrier-permeable multicomponent nanoscintillators that generate singlet oxygen upon X-ray interaction. Surface-modified scintillators interact selectively with Aβ and, upon X-ray irradiation, inhibit the formation of neurotoxic aggregates both in vitro and in vivo. Feeding transgenic Caenorhabditis elegans expressing human Aβ with the nanoscintillators and subsequent irradiation with soft X-ray reduces Aβ oligomer levels, extends lifespan, and restores memory and behavioral deficits. These findings support the potential of X-ray-based therapy for AD and warrant further development.

Senapati, S., Secchi, V., Cova, F., Richman, M., Villa, I., Yehuda, R., et al. (2023). Noninvasive Treatment of Alzheimer's Disease with Scintillating Nanotubes. ADVANCED HEALTHCARE MATERIALS, 12(32 (December 27, 2023)) [10.1002/adhm.202301527].

Noninvasive Treatment of Alzheimer's Disease with Scintillating Nanotubes

Secchi V.;Cova F.
Co-primo
;
Villa I.
Secondo
;
Campione M.
Penultimo
;
Monguzzi A.
Ultimo
2023

Abstract

Effective and accessible treatments for Alzheimer's disease (AD) are urgently needed. Soluble Aβ oligomers are identified as neurotoxic species in AD and targeted in antibody-based drug development to mitigate cognitive decline. However, controversy exists concerning their efficacy and safety. In this study, an alternative strategy is proposed to inhibit the formation of Aβ oligomers by selectively oxidizing specific amino acids in the Aβ sequence, thereby preventing its aggregation. Targeted oxidation is achieved using biocompatible and blood-brain barrier-permeable multicomponent nanoscintillators that generate singlet oxygen upon X-ray interaction. Surface-modified scintillators interact selectively with Aβ and, upon X-ray irradiation, inhibit the formation of neurotoxic aggregates both in vitro and in vivo. Feeding transgenic Caenorhabditis elegans expressing human Aβ with the nanoscintillators and subsequent irradiation with soft X-ray reduces Aβ oligomer levels, extends lifespan, and restores memory and behavioral deficits. These findings support the potential of X-ray-based therapy for AD and warrant further development.
Articolo in rivista - Articolo scientifico
Alzheimer's disease; Aβ amyloids; hybrid materials; nanoscintillators; singlet oxygen; X-rays;
English
12-ott-2023
2023
12
32 (December 27, 2023)
e2301527
open
Senapati, S., Secchi, V., Cova, F., Richman, M., Villa, I., Yehuda, R., et al. (2023). Noninvasive Treatment of Alzheimer's Disease with Scintillating Nanotubes. ADVANCED HEALTHCARE MATERIALS, 12(32 (December 27, 2023)) [10.1002/adhm.202301527].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/451719
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