Department of Chemistry, Research Center for Industries of the Future, Westlake University, 600 Dunyu Road, Hangzhou 310030, Zhejiang Province, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
Chem Rev. 2023 Nov 8;123(21):12254-12311. doi: 10.1021/acs.chemrev.3c00494. Epub 2023 Oct 24.
Protein misfolding and aggregation, a key contributor to the progression of numerous neurodegenerative diseases, results in functional deficiencies and the creation of harmful intermediates. Detailed visualization of this misfolding process is of paramount importance for improving our understanding of disease mechanisms and for the development of potential therapeutic strategies. While studies using purified proteins have been instrumental in delivering significant insights into protein misfolding, the behavior of these proteins in the complex milieu of living cells often diverges significantly from such simplified environments. Biomedical imaging performed in cell provides cellular-level information with high physiological and pathological relevance, often surpassing the depth of information attainable through methods. This review highlights a variety of methodologies used to scrutinize protein misfolding within biological systems. This includes optical-based methods, strategies leaning on mass spectrometry, in-cell nuclear magnetic resonance, and cryo-electron microscopy. Recent advancements in these techniques have notably deepened our understanding of protein misfolding processes and the features of the resulting misfolded species within living cells. The progression in these fields promises to catalyze further breakthroughs in our comprehension of neurodegenerative disease mechanisms and potential therapeutic interventions.
蛋白质错误折叠和聚集是导致许多神经退行性疾病进展的关键因素，导致功能缺陷和有害中间产物的产生。详细观察这种错误折叠过程对于提高我们对疾病机制的理解和开发潜在的治疗策略至关重要。虽然使用纯化蛋白的研究为深入了解蛋白质错误折叠提供了重要的见解，但这些蛋白质在活细胞复杂环境中的行为往往与简化环境有很大的不同。在细胞中进行的生物医学成像提供了具有高度生理和病理相关性的细胞水平信息，通常超过通过其他方法获得的信息深度。本综述强调了用于在生物系统中仔细研究蛋白质错误折叠的各种方法。这包括基于光学的方法、依赖质谱的策略、细胞内核磁共振和冷冻电子显微镜。这些技术的最新进展显著加深了我们对蛋白质错误折叠过程以及活细胞中产生的错误折叠物种特征的理解。这些领域的进展有望促进我们对神经退行性疾病机制和潜在治疗干预措施的理解取得进一步突破。
