D'Avanzo Carla, Aronson Jenna, Kim Young Hye, Choi Se Hoon, Tanzi Rudolph E, Kim Doo Yeon
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Biomedical Omics Group, Korea Basic Science Institute, Cheongju-si, Chungbuk, Republic of Korea.
Bioessays. 2015 Oct;37(10):1139-48. doi: 10.1002/bies.201500063. Epub 2015 Aug 7.
Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The "β-amyloid cascade hypothesis" of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery.
阿尔茨海默病（AD）是痴呆症最常见的病因，目前尚无治愈方法。AD的“β-淀粉样蛋白级联假说”是当前对AD发病机制及药物研发理解的基础。然而，尚无AD模型能完全验证这一假说。我们最近通过在三维（3D）细胞培养系统中培养基因修饰的人类神经干细胞，开发出了一种AD的人类干细胞培养模型。这些细胞能够重现AD病理学的关键事件，包括β-淀粉样蛋白斑块和神经原纤维缠结。在本综述中，我们将讨论AD小鼠模型和人类干细胞模型的进展及当前局限性，同时探索3D细胞培养系统的突破。我们还将分享我们对于神经退行性疾病培养皿模型在研究致病级联反应和治疗药物研发方面潜力的看法。
