September 4, 2021
The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance of these metal ions in the brain is closely related to the onset and progression of Alzheimer’s disease (AD), the most common neurodegenerative disorder in the elderly.
The metal ions imbalance induces Aβ and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition.
Calcium is one of the highest metal ions (~ 1200 g) in adult human body. The extracellular concentration of Ca2+ is 10− 3 M, which is almost ten-thousand times higher than that of the intracellular Ca2+ (10− 7 M). As a common second messenger, cellular calcium homeostasis plays a pivotal role in regulating many neuronal functions, including neural growth and differentiation, action potential, synaptic plasticity, and learning and memory. In AD experimental models, the intraneuronal calcium concentration is increased, and an elevated calcium level generally appear to be toxic to the cells and it triggers subsequent pathological processes of AD.
Erroneous DEPOSITION OF IRON, copper, zinc, or ELEVATION OF CALCIUM in different brain regions can promote Aβ overproduction, tau hyperphosphorylation and their aggregation/accumulation.
Current understanding of metal ions in the pathogenesis of Alzheimer’s disease