贝沙罗汀,小鼠AD新模型 z-bo 2020-09-01 369

　　The cancer drug bexarotene (bexarotene) has shown therapeutic effects in mice with Alzheimer’s disease, but it has been confusing in a new mouse model of AD (bexarotene) As a result, bexarotene is a mouse with advanced Alzheimer's disease. It may decrease the level of neurotoxic protein-β-amyloid, but it will increase the level of new β-amyloid in the early stages of AD disease. ) The AD model is more humane than Alzheimer's disease. It more closely mimics the genetic and pathological mechanisms of the disease.

　　University of Illinois researcher Mary Jo LaDu’s discovery was made at the International Conference on Alzheimer’s Disease in Copenhagen on July 16. MaryJoLaDu developed transgenic mice in 2012. It is considered to be the best animal model for simulating human diseases. The genes carried by experimental mice can increase the risk of AD by 15 times, making it the most important known genetic risk factor for the disease. Alzheimer's disease is the most common form of dementia, affecting more than 5 million Americans. The disease progresses slowly and eventually leads to death. One of the hallmarks of AD is the formation of dense plaques by β-amyloid in the brain. However, recent studies have shown that it is a smaller, soluble form of beta-amyloid, rather than solid plaque, which is responsible for neuronal death and cause cognitive decline. Apolipoprotein E (ApoE) binds to β-amyloid and breaks down to eliminate brain amyloid. LaDu said: Apolipoprotein E APOE4 is the biggest genetic risk factor for Alzheimer's disease. Previous studies have shown that compared with APOE3, the apolipoprotein produced by the apolipoprotein E4 gene cannot bind well to amyloid and therefore cannot remove toxins (amyloid) from the brain. About Bexarotene

　　"The results of studies on the effects of AD in mice are mixed, but have not been studied in mice with progressive AD-like diseases carrying the human APOE gene. Mary Jo LaDu of the University of Illinois conducted such preliminary research. In the early, middle or late stages of AD, LaDu and colleagues administered bexarotene to mice carrying apolipoprotein E4 or APOE3 for 7 days. The researchers then measured the level of soluble beta-amyloid in the mouse brain. In the late stage of AD disease in mice carrying human apolipoprotein E4, the researchers found that soluble β-amyloid was reduced by 40%, and β-amyloid bound to apolipoprotein increased. However, in mice carrying apolipoprotein E4 or APOE3, the amount of soluble β-amyloid in the early stages of AD actually increased. Researchers administered bexarotene to apolipoprotein E4 mice for one month after the onset of AD, analyzed whether the drug can prevent disease progression, and found that the drug had no beneficial effect. In the late stage of AD, bexarotene can be used for short-term treatment. However, further research is needed to determine the duration of treatment and the start time of treatment, and more importantly, whether APOE3 carriers also benefit from the drug. Bexarotene is highly toxic to the liver. Unless the dose is carefully controlled and the patient is carefully monitored, it is important to prevent the disease by taking bexarotene for a long time before symptoms of Alzheimer's disease appear. This is almost impossible because the liver toxicity of the drug is known.