老年痴呆实验动物模型研制进展.pptVIP

老年痴呆实验动物模型研制进展 Research Progress of Animal Models for Alzheimer’s Disease 张 斌 (Bin Zhang) M.D., Ph.D. 老年痴呆神经病理Neuropathology of AD 理想的老年痴呆实验动物模型标志 Idea AD Animal Models 老年痴呆实验动物模型种类Types of AD Animal Models 老年痴呆实验动物模型种类(续)Types of AD Animal Models 老年痴呆实验动物模型种类(续)Types of AD Animal Models Tau基因的变异Mutations in the Tau Gene 正常 Tau蛋白的功能Normal Tau Protein 正常Tau旦白的功能: 稳定微管并维持正常的神经元轴突转运Normal Tau Stabilizes MTs To Maintain Neuronal Transport  RW Tau 蛋白的分布改变: 从轴突到细胞体 RW Tau 蛋白的分布改变: 从轴突到细胞体Absence of Tau Staining in the Massy Fibers of Hippocampus in RW Mice 微管稳定药物MT Stabilizing Drugs TaxolR (Paclitaxel, mw 854) -isolated in 1971 from plant, the pacific yew Taxus brevifonia -the first of a class of MT stabilizing drug which was approved for use in the treatment of breast, ovarian and lung cancers; -appears to arrest cells in mitosis by stabilizing spindle MTs. -induce MT polymer mass in cell and “MT bundling”; -readily soluble in methanol, but limited soluble in water; PaxceedTM -A new MT Stabilizing anti-neoplastic agent by Angiotech Inc.; -In contrast to Taxol (Cremaphor formulation), PaxceedTM is a Micellar formulation that does not cause the inflammatory reactions; -Micellar paclitaxel is soluble in saline and once in the bloodstream, the micelles break down so that the paclitaxel can bind to serum albumin for bioavailability. 低剂量微管稳定药物改善轴突转运Fast Axonal Transport in the Ventral Root o is Improved in the Low Dose of PaxceedTM Treated T44 Tg Mice 中等剂量微管稳定药物改善轴突转运 Fast Axonal Transport in the Ventral Root is Improved in the Medium Dose of PaxceedTM Treated T44 Tg Mice 大剂量微管稳定药物减缓轴突转运 Fast Axonal Transport in the Ventral Root is Retarded in the High Dose of PaxceedTM Treated T44 Tg Mice MTs in the VR Axons of the Tau Tg Mice Treated with PaxceedTM The Numbers of MTs in the VR Axons Increase in the tau Tg Mice Treated with PaxceedTM Stable Detyrosinated Tubulin is Increased in