阿尔茨海默氏病,基因疗法,动物实验 z-bo 2020-09-24 370

　　Recently, a study from Imperial College London, UK, provides new possibilities for the treatment of Alzheimer's disease. The researchers said that their mouse experiments showed that gene therapy may be able to successfully treat Alzheimer's disease.

　　Alzheimer's disease is one of the most important global public health and social health challenges facing mankind today and in the future. According to the data in the "World Alzheimer's Disease Report 2015", there were 46.8 million people with Alzheimer's disease worldwide in 2015, which is expected to reach 74.7 million in 2030, and it is more likely to exceed 131.5 million in 2050 people.

　　Recently, a study from Imperial College London, UK, has provided new possibilities for the treatment of Alzheimer's disease. The researchers said that their mouse experiments show that gene therapy may be successful in treating Alzheimer's disease. However, some experts emphasized that whether this finding is applicable to humans requires further research. The results of this research were published in the Proceedings of the National Academy of Sciences.

　　The new possibility of gene therapy

　　Magdalena Sast, a researcher at Imperial College London who participated in the study, said that they used a modified lentiviral vector to inject a gene called PGC1-α into the memory area of the mouse brain. The mice just started showing early symptoms of Alzheimer's disease. The results showed that this therapy prevented the accumulation of β-amyloid in the mouse brain, which is thought to cause the death of brain cells and is closely related to the onset of Alzheimer's disease.

　　Researchers said that after 4 months of gene therapy treatment, these mice had very few amyloid plaques that are hallmarks of Alzheimer's disease. In task tests related to memory, these treated mice performed equally well as healthy mice. In addition, no brain cell loss was found in their brain memory area.

　　Saster said in a statement: "Although these findings are still in a very early stage, they show that gene therapy may have the potential to treat patients with Alzheimer's disease." Saster emphasized that there are still many Difficulties need to be overcome, but "this proof-of-concept study shows that this approach is worth further exploration."

　　Some experts who did not participate in the research said that this research has important scientific value, but mice cannot be equated to humans, so it should be interpreted with caution. For example, Tara Spears-Jones, interim director of the Centre for Cognitive and Nervous System at the University of Edinburgh, said that this study is based on only a small number of mice in one disease model. “These results require multiple models to be able to replicate and overcome There are many difficulties to know whether this therapy can be used for human patients."

　　The two most obvious genes

　　Genetic factors have an important influence on the incidence of Alzheimer's disease. Preston Estep, the head of geriatric research in the "Personal Genome Project" at Harvard Medical School in the United States and author of "Genes for Longevity," told the reporter of "China Science News" that two of these genes are most obvious , That is apolipoprotein E (APOE) and amyloid precursor protein (APP).

　　"There are three variants of APOE, e2, e3, and e4. Everyone will carry two copies of APOE, and each copy may be in any of the three variants mentioned above. In other words, the human body carries APOE. There are 6 possible forms of copy, namely e2/e2, e2/e3, e2/e4, e3/e3, e3/e4, e4/e4." Estep said that e3/e4 will affect individuals with Al The risk of Zheimer's disease increases two to three times, and e4/e4 will increase this risk by as much as ten times. In the United States, the number of people carrying copies of the e4/e4 gene accounts for about 2% of the total population, but they account for 15% of the total number of patients with Alzheimer's disease. But it should be noted that there are some minorities, including people of African descent, who are usually immune to the negative effects of this genetic variant. Among the world's population, those carrying e3 variants are the most common.

　　"APP is a single-pass transmembrane protein widely present in tissues and cells throughout the body. Studies have found that the main function of APP is to protect cells and tissues in the brain from iron oxidation damage." Estep said, " The variation of APP is the main cause of senile plaques in the brains of Alzheimer's disease patients, which is the accumulation of β-amyloid protein to form plaques."

　　Estep explained that in the 1980s, scientists discovered APP while studying Down syndrome. APP is located on chromosome 21. The three gene copies of APP produce excessive amyloid preprotein, which accelerates the formation of β-amyloid plaques. "This also explains why individuals with Down syndrome often develop Alzheimer's disease early in their 30s and 40s."

　　Gene and environmental factors interact

　　Estepp emphasized that the influence of diet and lifestyle on the pathogenic effects of these two genes should not be underestimated, such as their interaction with iron in the human body.

　　"Specific parts of the brain and nervous system are very sensitive to iron. In adolescence, iron is a key nutrient element that promotes brain development. However, after entering adulthood, excessive iron may cause a person's cognitive ability to begin Decline increases the risk of brain and nervous system diseases such as Alzheimer’s disease and Parkinson’s disease." Estep said, "Iron is like firewood. Within the controllable range, it can bring We are bright and warm, but if we lose control, wildfires may spread."

　　"More and more research evidence shows that APOE is responsible for the transport of iron to the brain. As the accumulation of iron increases, APP protein is also increasing to protect the cells and tissues in the brain. The special cleansing cells will start to work. A small part of the APP will be cut and discarded. The discarded part is β-amyloid, which is the culprit in the formation of senile plaques in the brain. The tailoring enzymes will be in the cell Play other functions, but the cut APP has no meaning to the human body, and may even cause collateral damage to the human body. With the accumulation of β-amyloid protein, functional brain cells will be killed and replaced." For APOE and APP The interaction between these two genes and iron is explained by Estep.

　　In Estep's view, the negative effects of this process may seem insignificant at first, but after accumulating year by year, they will become apparent when a person reaches the age of 70 or 80. "For ordinary people, it is easier to adjust environmental factors to prevent Alzheimer's disease than using gene therapy, such as not excessive intake of iron, which reduces the risk of Alzheimer's disease. A good way of chance."

　　Although it is not difficult to control iron intake, Estep also expressed concern about this. "Because iron has a good reputation for being ubiquitous and inexplicable. When you are listless, people may not recommend you to supplement sleep or improve the quality of sleep, but they may recommend you to supplement some iron." Said helplessly.

　　In this regard, Esteppe suggested that everyone should pay more attention to the iron content in food. "For women who are menstruating normally, 18mg of iron can provide them with 100% of their daily intake. For other adults, generally 8mg of iron per day is sufficient." Ace Tepp also said, “People have individual differences in the absorption efficiency of iron. In addition to paying attention to the iron content in food and reasonably controlling the intake, it can also monitor key biomarkers for measuring iron, including serum iron. , Serum ferritin, hemoglobin, etc."