铁代谢异常,阿尔茨海默氏病,老年痴呆 z-bo 2020-09-15 372

　　The results of Meta analysis by Wang Fuquan’s research group at Zhejiang University School of Public Health fully affirmed the close relationship between abnormal iron metabolism and Alzheimer’s, and fundamentally subverted the traditional view that “iron overload is a typical characteristic of Alzheimer’s patients” and passed Sufficient data confirm that patients with Alzheimer's disease are low in serum iron, and are often accompanied by (mild) iron deficiency anemia, and there is high iron accumulation in specific brain areas. The research results suggest that the imbalance of iron homeostasis in the body plays a key role in the occurrence and development of Alzheimer’s, and preventing or reducing the accumulation of high-speed iron in brain tissue is an important measure for the prevention and treatment of Alzheimer’s.

　　The essential trace element iron is an important raw material for the synthesis of hemoglobin and myoglobin in the body. It is also a coenzyme for many enzymes in a series of redox reaction systems, and it participates in important physiological processes such as oxygen transport and cellular respiration. Therefore, the regulation of iron homeostasis metabolism plays an important role in maintaining the body's metabolism. Iron deficiency can cause cell growth to stagnate or even die, and the human body exhibits symptoms of anemia. However, excessive iron is also harmful to cells. Excess iron will generate free radicals and further damage cell components such as DNA, protein and liposomes, and affect cell function. It is precisely because of the cytotoxic effect of high-speed iron that the issue of whether the accumulation of high-speed iron contributes to Alzheimer's disease has attracted the attention of the scientific community as early as the 1990s.

　　Alzheimer’s disease, also commonly referred to as Alzheimer’s disease, is a neurodegenerative disease characterized by progressive cognitive dysfunction. Its typical neuropathological changes are β-amyloid protein (β- amyloid, Aβ) deposition and neurofibrillary tangles (NFTs) in neuronal cells. Studies have found that iron can selectively accumulate in the brain regions where Aβ is deposited; other studies have shown that there is an excess of iron in neuronal cells with fibrillary tangles. In recent years, the latest published research has also provided important evidence for the association between iron and Alzheimer’s. That is, the mRNA of the precursor protein APP of Aβ amyloid precipitation has iron-responsive elements, and its translation process is regulated by iron content, and APP protein It also has iron oxidizing activity, which can oxidize divalent iron to trivalent, thereby promoting iron excretion from neuronal cells (Duce JA, et al. Cell. 2010); multiple studies have also found that iron metabolism gene mutations are associated with Alzheimer’s The risk of morbidity is positively correlated (Wang Y, et al. Can J Neurol Sci. 2013). These studies suggest that iron metabolism plays a role in the occurrence and development of Alzheimer's disease.

　　In order to further clarify the role of iron homeostasis in the occurrence of Alzheimer's disease, Wang Fuquan's research group carried out a meta-analysis study based on this. Under the guidance of Professor Wang Fuquan, PhD student Tao Yunlong identified 2556 relevant research reports through database search; then selected 105 papers for further analysis through the thesis title and abstract screening; finally 43 research documents were included in the comprehensive in-depth analysis. The study conducted a systematic meta-analysis of iron levels in serum, cerebrospinal fluid and 12 brain regions of patients with Alzheimer’s disease and found that serum iron levels in Alzheimer’s patients were significantly lower than those of normal controls, and there was no significant difference in iron content in cerebrospinal fluid. . A more significant finding is that there is high-speed iron accumulation in the brain tissue of patients with Alzheimer’s. The high-speed iron accumulation is not all over the whole brain area. The iron content in 12 brain areas shows different trends. Iron is selectively located in the frontal, parietal, and The temporal lobe, amygdala, caudate putamen, globus pallidus, and caudate nucleus are highly accumulated in 7 specific brain regions.

　　The study reveals a new law of abnormal iron metabolism in patients with Alzheimer’s from a new perspective. Although the mechanism of this specific brain region of high iron accumulation is not clear, it has been fully confirmed that the treatment of Alzheimer’s cannot simply adopt a low-iron diet or systemic treatment. Iron treatment, preventing the accumulation of high-speed iron in specific brain areas and removing iron treatment in specific brain areas are the fundamental measures for the prevention and treatment of Alzheimer's disease.

　　The research was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, Zhejiang University and the Chinese Academy of Sciences.