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阿尔茨海默病相关的金属内稳态平衡调控研究
Metals Homeostasis and Related Proteins in Alzheimer’s Disease
阿尔茨海默病(AD),俗称老年痴呆症,是一种老年神经退行性疾病,其病理特征为脑神经细胞间隙的老年斑(senile plaques, SP)、神经细胞内的神经纤维缠结(neurofibrillary tangles, NFTs)、神经元数量减少和颗粒空泡变性。尽管AD的发病机理十分复杂,但是淀粉样多肽(Aβ)、淀粉样前体蛋白(APP)、金属硫蛋白-3(MT3)及其所参与调节的金属离子内稳态平衡与 AD 的发生发展有着密切的联系。过渡金属离子如铜和锌,在人体正常的生理过程中发挥着重要的作用, 而在阿尔茨海默病患者的大脑内,金属内稳态失衡可能是阿尔茨海默病的主要诱因之一。金属内稳态的失衡会影响淀粉样多肽的聚集以及活性氧物种(ROS)的产生,进而产生细胞毒性;而金属硫蛋白-3(MT3)参与调节大脑金属稳态平衡,具有解聚淀粉样多肽,降低神经细胞毒性的作用。本文综述了大脑过渡金属铜、锌、铁稳态平衡及其调控机制有关的研究进展。
Alzheimer’s disease (AD) is a kind of neurodegenerative diseases often found in old people. The characteristic pathological features of Alzheimer’s disease are senile plaques, neurofibrillary tangles, the loss of neurons,and granulovacuolar degeneration. Though the mechanism of Alzheimer’s disease is very complicated and not understood clearly, the metal homeostasis,which amyloid beta, amyloid precursor protein and metallothionein-3 participated in, is associated with the development of Alzheimer’s disease. The transitional metals, such as copper and zinc, play a key role in the physiologic function. Abnormally high levels of metals were found in the brain of Alzheimer’s disease patients compared with the healthy people. The aberrant of metal homeostasis may be one of the reasons that induce Alzheimer’s disease. The imbalance of metal homeostasis in the brain of Alzheimer’s disease leads to the aggregation of amyloid beta and the generation of reactive oxygen species. The copper can generate reactive oxygen species via Fenton type reaction, resulting in toxicity to the cells. Metallothionein-3, as a metal homeostasis regulator, can protect against the neuronal toxicity of Aβ by preventing copper-mediated Aβ aggregation, abolishing the production of reactive oxygen species(ROS). This review focuses on the AD research progress regarding the metal homeostasis regulation with some related proteins.
Contents
1 Introduction
2 Metals homeostasis in the brain and Alzheimer’s disease
2.1 Copper homeostasis and Alzheimer’s disease
2.2 Zinc homeostasis and Alzheimer’s disease
2.3 Iron homeostasis and Alzheimer’s disease
3 Amyloid beta and Alzheimer’s disease
4 Amyloid precursor protein and Alzheimer’s disease
5 Metallothionein-3 and Alzheimer’s disease
6 Outlook
阿尔茨海默病
Alzheimer’s disease
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