Metal ions influx is a double edged sword for the pathogenesis of Alzheimer's disease.
Alzheimer's disease (AD) is a common form of dementia in aged people, which is defined by two pathological characteristics: β-amyloid protein (Aβ) deposition and tau hyperphosphorylation. Although the mechanisms of AD development are still being debated, a series of evidence supports the idea that metals, such as copper, iron, zinc, magnesium and aluminium, are involved in the pathogenesis of the disease. In particular, the processes of Aβ deposition in senile plaques (SP) and the inclusion of phosphorylated tau in neurofibrillary tangles (NFTs) are markedly influenced by alterations in the homeostasis of the aforementioned metal ions. Moreover, the mechanisms of oxidative stress, synaptic plasticity, neurotoxicity, autophagy and apoptosis mediate the effects of metal ions-induced the aggregation state of Aβ and phosphorylated tau on AD development. More importantly, imbalance of these mechanisms finally caused cognitive decline in different experiment models. Collectively, reconstructing the signaling network that regulates AD progression by metal ions may provide novel insights for developing chelators specific for metal ions to combat AD.
College of Life and Health Sciences, Northeastern University, No. 3-11, Wenhua Road, Shenyang, 110819, PR China. Electronic address: wangpu@mail.neu.edu.cn.
Pu
P
Wang
College of Life and Health Sciences, Northeastern University, No. 3-11, Wenhua Road, Shenyang, 110819, PR China. Electronic address: wangzy@mail.neu.edu.cn.
Zhan-You
ZY
Wang
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001343:Autophagy; D003300:Copper / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000473:pathology; D009473:Neuronal Plasticity / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000473:pathology; D015032:Zinc / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D008670:Metals; D016875:tau Proteins; D003300:Copper; D015032:Zinc
Alzheimer’s disease; Apoptosis; Autophagy; Cognitive decline; Metal ions; Neurotoxicity; Oxidative stress; Synaptic plasticity