Aβ40 Aggregation under Changeable Conditions

Jofre Seira Curto, Maria Rosario Fernandez, Josep Cladera, Núria Benseny-Cases, Natalia Sanchez de Groot

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Abstract

Homeostasis is crucial for cell function, and disturbances in homeostasis can lead to health disorders. Under normal conditions, intracellular pH is maintained between 7.35 and 7.45. Altered endosomal and lysosomal pH together with a general drop in brain pH are associated with the aggregation of amyloid-β-peptide (Aβ) and the development of Alzheimer’s disease. Under acidic conditions, close to the Aβ isoelectric point, the absence of charges favors the formation of intermolecular contacts and promotes aggregation. Here, we analyzed how pH levels affect the aggregation of Aβ40 considering the variations in brain pH and the coexistence of different aggregated conformations. Our results suggest that different macromolecular conformations can interact with each other and influence the aggregation process. In addition, we showed that neutral pH and physiological salt concentrations favor a slow aggregation, resulting in ordered, stable fibrils, with low cytotoxic effects. Overall, we highlight the complexity of the aggregation processes occurring in different physiological and pathological environments.
Original languageEnglish
Article number8408
Number of pages13
JournalInternational journal of molecular sciences
Volume24
Issue number9
DOIs
Publication statusPublished - 7 May 2023

Keywords

  • aggregation
  • amyloid-β-peptide
  • charge repulsion

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