Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bld 35A, Room 1E623 35 Convent Drive, MSC 3708, Rockville, MD 20892, USA.
Aligning Science Across Parkinson's (ASAP) Collaborative Network, Chevy Chase, MD 20815, USA.
Biomolecules. 2022 Apr 21;12(5):616. doi: 10.3390/biom12050616.
Lysosomes are ubiquitous membrane-bound organelles found in all eukaryotic cells. Outside of their well-known degradative function, lysosomes are integral in maintaining cellular homeostasis. Growing evidence has shown that lysosomal dysfunction plays an important role not only in the rare group of lysosomal storage diseases but also in a host of others, including common neurodegenerative disorders, such as Alzheimer disease and Parkinson disease. New technological advances have significantly increased our ability to rapidly isolate lysosomes from cells in recent years. The development of the Lyso-IP approach and similar methods now allow for lysosomal purification within ten minutes. Multiple studies using the Lyso-IP approach have revealed novel insights into the pathogenic mechanisms of lysosomal disorders, including Niemann-Pick type C disease, showing the immense potential for this technique. Future applications of rapid lysosomal isolation techniques are likely to greatly enhance our understanding of lysosomal dysfunction in rare and common neurodegeneration causes.
溶酶体是普遍存在于所有真核细胞中的膜结合细胞器。除了其众所周知的降解功能外,溶酶体在维持细胞内稳态方面也起着重要作用。越来越多的证据表明,溶酶体功能障碍不仅在罕见的溶酶体贮积病群体中发挥重要作用,而且在许多其他疾病中也发挥重要作用,包括常见的神经退行性疾病,如阿尔茨海默病和帕金森病。新技术的进步近年来极大地提高了我们从细胞中快速分离溶酶体的能力。Lyso-IP 方法和类似方法的发展现在允许在十分钟内进行溶酶体纯化。使用 Lyso-IP 方法的多项研究揭示了溶酶体疾病发病机制的新见解,包括尼曼-匹克 C 型疾病,显示了该技术的巨大潜力。快速溶酶体分离技术的未来应用可能会极大地提高我们对罕见和常见神经退行性疾病中溶酶体功能障碍的理解。