Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics

EC Pharmacol Toxicol. 2019 Jul;7(7):547-558. Epub 2019 Jun 21.

Abstract

Alzheimer's disease (AD) characterized by insoluble amyloid-β (Aβ) deposits, neurofibrillary tangles (NFTs), and neuronal demise. The influence of environmental and genetic factors on AD progression remains elusive, however evidence suggests biometal dyshomeostasis elicits neuronal death, neuroinflammation, and accumulated oxidative damages in AD brain. As such, three pathways have been identified that result from abnormal biometal accumulation and increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in AD brain parenchyma: (1) the damage caused by direct oxidation of cellular components such as DNA and proteins; (2) the oligomerization of Aβ and NFTs, and (3) the promotion of apoptosis through NF-κB signaling pathway. Finally, given recent developments in nanotechnology, we have briefly reviewed potential nanotheranostic agents as potential AD theranostics.

Keywords: Alzheimer’s Disease; Aβ Amyloid; Biometals; Blood-Brain Barrier; Metal Chelators; Nanotheranostics; Redox Stress; Tau Protein.