Title
Amyloid Cascade Hypothesis for Alzheimer’s Disease. Does It Work Under Physiological Conditions?
Document Type
Article
Journal Title
Precision Nanomedicine
Publication Date
2023
Volume
6
Abstract
Plaques in the brain consisting of proteins are a hallmark of diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such aggregates can be assembled spontaneously by specialized proteins such as amyloid beta (Ab) proteins in the case of AD. Numerous in vitro studies made a foundation for the Amyloid Cascade Hypothesis (ACH), according to which the misfolding of proteins leads to their self-assembly into toxic oligomers along with the formation of amyloid fibrils assembled as plaques in the brain. Notably physiological concentration of Ab proteins in the brain is in the low nanomolar concentration, so no spontaneous aggregation of Ab protein occurs at such conditions, questioning the validity of the ACH model. However, recent studies revealed that surfaces could play a role as a catalyst of the aggregation process, so self-assembly of Ab can be observed at physiologically low concentrations of Ab proteins, although no spontaneous aggregation occurs in the bulk solution. The catalytic property of membrane surfaces towards Ab aggregation depends on the membrane composition. This finding suggests a number of novel ideas on molecular mechanisms of amyloid selfassembly, which lay a foundation for the development of treatments and preventions for AD, as discussed in this article.
DOI Link
ISSN
2639-9431
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Lyubchenko, Yuri L., "Amyloid Cascade Hypothesis for Alzheimer’s Disease. Does It Work Under Physiological Conditions?" (2023). Journal Articles: Pharmaceutical Sciences. 44.
https://digitalcommons.unmc.edu/cop_pharmsci_articles/44