动物造模,阿尔兹海默症 z-bio 2021-12-24 271

　　Alzheimer's disease (Alzheimer's disease, AD), commonly known as Alzheimer's, is a chronic degenerative brain degenerative disease that occurs in the old and pre-senile period. The main characteristics are progressive memory loss, cognitive impairment, personality changes, etc. . With the extension of human life span, the incidence of AD is increasing year by year, and it has become the fourth leading cause of death in the elderly after tumors, heart disease, and cerebrovascular diseases. At present, the commonly accepted pathogenesis of AD are: cholinergic theory, β-amyloid cascade theory, tau protein hypothesis, oxidative stress theory, etc. There is no effective treatment drug for AD. The existing drugs mainly act to improve the function of the choline system, correct the imbalance of calcium homeostasis, interfere with the formation of Aβ, and help metabolism and anti-oxidation.

　　The optical transparency and small size of zebrafish juveniles make it the best model for in vivo imaging and drug development. Coupled with the characteristics of high-throughput, easy observation, and convenient quantitative analysis of zebrafish behavior analysis, zebrafish are increasingly used in the research of neurological diseases based on behavioral analysis and the development of neurological drugs. As more researchers apply zebrafish to the field of AD research, genes related to the onset of AD have been discovered in zebrafish. Studies on the γ-secretase and β-secretase in the classic β-amyloid pathway have been in-depth. In view of the new hot spot Tau protein in recent AD research, zebrafish are used by more researchers because of their convenient genetic manipulation and easy observation.

　　For example, Tomasiewicz et al. injected green fluorescently labeled human tau protein directly into zebrafish embryos and found neurofibrillary tangles in the zebrafish brain (J Neurosci Res. 2002 Dec 15; 70(6)). Bai et al. of the University of Pittsburgh used the zebrafish's own promoter enolase-2 to regulate the human mutant 4Rtau to establish a Tg (enoZ:Tau) zebrafish model and found that neurofibrillary tangles appeared in the zebrafish spinal cord, axons and neuronal cells. Combining the advantages of zebrafish itself, a good animal model with operability, sensitivity, repeatability, and stability can be established. When AstraZeneca used zebrafish to develop drugs for Alzheimer’s disease, through reasonable drug design, it determined a highly effective GSK3β inhibitor——AR-534, which can reduce the phosphorylation level of tau protein in transgenic zebrafish, and you can see GSK3β After suppression, the zebrafish showed obvious deformities.

　　Huante Biotechnology has established a zebrafish AD model induced by AlCl3, which can be used to screen cholinergic targeted drugs. In this model, the activity of acetylcholinesterase is increased, and the level of acetylcholine is decreased, resulting in decreased cholinergic nervous system function and memory loss. In addition, Huante also established a β-amyloid (Aβ)-induced AD model for screening Aβ-targeted drugs. For detailed evaluation indicators, please refer to the official website of Huante Biology.