现代生物学仪器分析成果与应用3.PDF

现代生物学仪器分析现代生物学仪器分析 成果与应用成果与应用33 DirectDirect ThreeThree-dimensionaldimensional VisualizationVisualization of Membrane Disruption by Amyloid Fibrils Lilia Milanesi ，Tania Sheynis, Wei-Feng Xueb, Elena V. Orlovaa,Orlovaa, AndrewAndrew L.L. Hellewellb,Hellewellb, RazRaz Jelinekc,Jelinekc, EricEric W.W. Hewittb, Sheena E. Radford, and Helen R. Saibil. PNAS.2012 . ProteinProtein FibrillationFibrillation andand PathologyPathology of Amyloid Diseases Ⅰ: Monomer Intermediate Oligomer Amyloid fibril Ⅱ: Pathologygy Monomer Nucleation Nucleau Elongation Amyloid fibril Fibril fragmentation NucNucleaueau Add monomers Fibril Fragmentation Enhances Amyloid Cytotoxicity Wei-Feng Xue, Andrew L. Hellewell, Walraj S. Gosal, SteveSteve WW. HomansHomans, EricEric WW. HewittHewitt, andand SheenaSheena EE. Radford. JBC.2009 RodRod--likelike, WormWorm--likelike, ShortedShorted andand LongLong Fibrils Studied in this Article FibrilFibril FragmentationFragmentation Induced Cell Death Conclusion of the Article ?? HowHow doesdoes thethe fragmentedfragmented fibrils cause cell death? Direct Three-dimensional Visualization ofof MembraneMembrane DisruptionDisruption byby AmyloidAmyloid Fibrils Tomography of Lipsome-fibril InteractionInteraction MeasuredMeasured viavia CryoelectronCryoelectron and 3D Simulation 启示  他们的他们的JBC 的研究中发现了的研究中发现了 “纤维片段化可以纤维片段化可以 使纤维更有毒性”这个现象。但是，“一篇论 文解决了一个问题，又会引出新的问题”，他 们“顺藤摸瓜，寻根究底”，通过进一步研究 纤维和膜的相互作用，发了更好的文章 （（PNASPNAS ）），工作具有工作具有系统性和延续性系统性和延续性。  纤维对膜整合性的破坏为透析相关淀粉样病的 病理机制提供了病理机制提供了一种解释模式种解释模式，该机制可供该机制可供 Tau, prion, SOD1等蛋白质借鉴。  人工膜人工膜的研究方式有可借鉴之处的研究方式