小鼠AD新模型实验,沙罗汀治疗 z-bo 2020-11-03 561

　　Although a cancer treatment drug bexarotene (bexarotene) has shown therapeutic efficacy in Alzheimer's disease mice, it has obtained confusing results in a new mouse model of AD (the drug bexarotene) bexarotene can reduce the level of neurotoxic protein-β-amyloid in mice with advanced Alzheimer’s disease, but it increases the level of β-amyloid in the early stages of AD disease), new mice The AD model more closely mimics the genetic and pathological mechanisms of human Alzheimer's disease than any other animal model.

　　The discovery of Mary Jo LaDu, a researcher at the University of Illinois, was presented at the Alzheimer’s Association International Conference in Copenhagen on July 16. Mary Jo LaDu developed a genetically modified mouse in 2012, namely It is now considered the best animal model for simulating human diseases. The experimental mouse carries a gene that confers a 15-fold higher risk of AD in humans, 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. This disease is gradual and eventually leads to death. One of the characteristics of AD is that β-amyloid clumps in the brain form dense plaques. However, recent studies have shown that it is not solid plaques that are responsible for the death of nerve cells and cause cognitive decline, but small soluble forms of β-amyloid.

　　Apolipoprotein E (ApoE) binds to β-amyloid and breaks down β-amyloid to clear the brain amyloid. LaDu said: APOE4 in apolipoprotein E is the biggest genetic risk factor for Alzheimer's disease. Previous work has shown that compared to APOE3, the apolipoprotein produced by the apolipoprotein E4 gene does not bind to amyloid well, and therefore does not remove toxins (amyloid) from the brain.

　　Although the results of research on the effect of bexarotene on AD in mice have been mixed, there is no research conducted in mice carrying the human APOE gene with progressive AD-like pathology. Mary Jo LaDu from the University of Illinois conducted the first such study.

　　LaDu and their colleagues gave bexarotene to mice carrying apolipoprotein E4 or APOE3 for seven days in the early, middle or late stages of AD. 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 apolipoprotein binding β-amyloid increased. However, in the early stages of AD in mice carrying apolipoprotein E4 or APOE3, the amount of soluble β-amyloid actually increases. Researchers gave bexarotene to apolipoprotein E4 mice at the beginning of AD for a period of one month. They analyzed whether the drug can prevent the disease from getting worse, and found that the drug did not exert a beneficial effect.

　　Research suggests that it may be beneficial to give bexarotene in the late stage of AD disease in mice carrying the apolipoprotein E4 gene, and short-term treatment may be beneficial. However, further research is needed to determine the duration of treatment and the start time of treatment, and more importantly, to confirm whether APOE3 carriers will also benefit from the drug.

　　Bexarotene is extremely toxic to the liver. Unless the dose is carefully controlled and the patient is closely monitored, it is almost impossible to prevent disease, that is, to give the drug bexarotene for a longer period of time before the symptoms of Alzheimer's disease appear. Impossible, this is because of the known liver toxicity of the drug.