Preparation and Characterization of Zn(II)-Stabilized Aß42 Oligomers.
ACS Chem Neurosci
; 15(14): 2586-2599, 2024 Jul 17.
Article
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| MEDLINE
| ID: mdl-38979921
ABSTRACT
Aß oligomers are being investigated as cytotoxic agents in Alzheimer's disease (AD). Because of their transient nature and conformational heterogeneity, the relationship between the structure and activity of these oligomers is still poorly understood. Hence, methods for stabilizing Aß oligomeric species relevant to AD are needed to uncover the structural determinants of their cytotoxicity. Here, we build on the observation that metal ions and metabolites have been shown to interact with Aß, influencing its aggregation and stabilizing its oligomeric species. We thus developed a method that uses zinc ions, Zn(II), to stabilize oligomers produced by the 42-residue form of Aß (Aß42), which is dysregulated in AD. These Aß42-Zn(II) oligomers are small in size, spanning the 10-30 nm range, stable at physiological temperature, and with a broad toxic profile in human neuroblastoma cells. These oligomers offer a tool to study the mechanisms of toxicity of Aß oligomers in cellular and animal AD models.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Zinc
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Péptidos beta-Amiloides
Límite:
Humans
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido