Abstract
Evidence of copper’s (Cu) involvement in Alzheimer’s disease (AD) is available, but information on Cu involvement in microglia and astrocytes during the course of AD has yet to be structurally discussed. This review deals with this matter in an attempt to provide an updated discussion on the role of reactive glia challenged by excess labile Cu in a wide picture that embraces all the major processes identified as playing a role in toxicity induced by an imbalance of Cu in AD.
Highlights
Evidence of copper’s (Cu) involvement in Alzheimer’s disease (AD) is available, but information on Cu involvement in microglia and astrocytes during the course of AD has yet to be structurally discussed
TNF-α inflammatory signaling promotes the degradation of IκB, which implies the elevated expression of NF-κB in the hippocampus and cerebral cortex. These findings suggest that inflammatory responses in activated microglial and neighboring neuronal cells aggravate the neurotoxicity that leads to the neurodegenerative process [166]
The evidence provided shows that aberrant glial cell biology might be involved in the deprivation of the physiological metal microenvironment around neurons, which can have direct injurious effects on functioning and viability of brain neuron cells
Summary
The pleiotropic pathogenesis of Alzheimer’s disease (AD), along with drugs developed in the “inside-out approach,” which relied heavily around halting/clearing intracellular aggregates of the hyper phosphorylated tau protein and extracellular plaques of the βamyloid (Aβ) peptide, led to the failure of most clinical trials despite decades of research. Thanks to the rapid development and improvement of imaging technologies and experimental research, attention has been diverted beyond the “classical neuronal death or β-amyloid cascade hypothesis” to the immediate surroundings around neurons, i.e., nonneuronal cells (glial cells) in neuronal health, aging, and AD (the outside-in approach) [1,2]. Microglia involvement is increasingly factored into sporadic AD pathogenesis [6,7]. Several mechanisms of Cu toxicity identified as contributing to AD onset and progression are briefly explained, with a focus on the involvement of microglia and astrocytes in the context of Cu imbalance playing a part in AD pathogenesis/development in a subset of AD patients.
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