Alzheimer's amyloid-beta as a preventive antioxidant for brain lipoproteins.
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Kontush A
Alzheimer's amyloid-beta as a preventive antioxidant for brain lipoproteins.
Cell Mol Neurobiol. 2001 Aug;21(4):299-315.
- PubMed ID
- 11775062 [ View in PubMed]
- Abstract
1. Increased production of A beta in a form of lipoprotein antioxidant under the action of increased oxidative stress in aging with subsequent chelation of transition metal ions by A beta, accumulation of toxic A beta-metal lipoprotein complexes, production of reactive oxygen species, and neurotoxicity are reviewed and postulated to form the temporal sequence of events in the development of Alzheimer's disease (AD). 2. Since (i) A beta binds copper stronger than iron and other transition metals, and (ii) copper is a more efficient catalyst of oxidation than other transition metals, chelation of copper by A beta is proposed to be a most important part of this pathway. 3. Whereas this amyloid-binds-copper (ABC) model does not remove A beta peptide from its central place in our current thinking of AD, it places additional factors in the center of discussion. 4. Most importantly, they embrace pathological mechanisms known to develop in aging (which is the most important risk factor for AD), such as increased production of reactive oxygen species by mitochondria, that can be positioned upstream relative to the generation of A beta.