Alzheimer's Research and Therapy Open Access (ARTOA)

ISSN: 2691-5790

Hypothesis

Amyloid B-Protein Aggregation at Physiologically Relevant Concentrations. A Critical Role of Membranes

Authors: Lyubchenko YL*

Abstract

Background: The aggregation of amyloid beta (Ab) is a self-assembly process that results in the production of fibrillar structures along with neurotoxic aggregates. However, in the vast majority studies in vitro the required Ab concentrations is several orders higher of the physiological relevant concentrations of Aβ; no aggregation is observed at physiological low nanomolar range of Aβ. This suggests that the assembly of Aβ in aggregates in vivo utilizes pathways different from those used in experiments in vitro. Results: The spontaneous assembly of Aβ oligomers within the physiologically relevant concentration range can occur, but it is the on-surface aggregation mechanism, in which the surface pays a role of the catalyst of the aggregation process. The model for the on-surface aggregation process suggests that the self-assembly of Aβ oligomers is initiated by the interaction of amyloid proteins with the cellular membrane. The membrane catalyzes amyloid aggregation by stabilizing an aggregationprone conformation of amyloids. The lipid composition contributes to the membrane-mediated misfolding and aggregation of Aβ monomers. Conclusion: Membrane-mediated aggregation catalysis explains a number of observations associated with the development of AD. The affinity of Aβ monomers to the membrane surface is the major factor defining the aggregation process rather than Aβ concentration. According to the model, the development of potential preventions for the interaction of monomeric amyloids with membrane can help control the aggregation process. This is a paradigm change for the development of efficient treatments, early diagnostics, and preventions for Alzheimer’s disease.

Keywords: Amyloid beta; Membrane composition; Oligomers; Alzheimer’s disease

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