Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, CanadaN6A 5C1.
Analyst. 2020 Apr 7;145(7):2473-2481. doi: 10.1039/c9an02270h. Epub 2020 Feb 17.
Gangliosides have a wide variety of biological functions due to their location on the outer leaflet of plasma membranes. They form a critical component of membrane rafts, or ganglioside-enriched microdomains, where they influence the physical properties of the membrane as well as its function. Gangliosides can change their structure to meet their external and internal environmental demands. This ability to change structure makes gangliosides both fascinating and technologically challenging targets to identify and understand. A full understanding on how gangliosides are regulated within the central nervous system (CNS) is critical, as ganglioside dysregulation is observed in the aging brain as well as in several neurodegenerative injuries and diseases such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease and several lysosomal storage disorders diseases, including Tay Sach's disease. Mass spectrometry (MS) has become a useful means to better understand ganglioside composition and function. Imaging mass spectrometry (IMS) provides the added benefit of placing analytical information within an anatomical context. This review article will discuss recent advances in MS-based detection methods, with a focus on IMS-based approaches to help understand the spatial-specific role gangliosides in the healthy brain as in CNS injuries and disease.
神经节苷脂因其位于质膜的外小叶而具有广泛的生物学功能。它们构成了膜筏或富含神经节苷脂的微区的关键组成部分,在那里它们影响膜的物理性质及其功能。神经节苷脂可以改变其结构以满足其外部和内部环境的需求。这种改变结构的能力使神经节苷脂成为令人着迷且具有技术挑战性的识别和理解目标。充分了解神经节苷脂在中枢神经系统 (CNS) 中的调节方式至关重要,因为在衰老的大脑以及几种神经退行性损伤和疾病(如中风、阿尔茨海默病、帕金森病、亨廷顿病和几种溶酶体贮积症疾病中,如泰萨氏症)中观察到神经节苷脂失调。质谱 (MS) 已成为更好地了解神经节苷脂组成和功能的有用手段。成像质谱 (IMS) 提供了将分析信息置于解剖学背景下的附加优势。本文综述了基于 MS 的检测方法的最新进展,重点介绍了基于 IMS 的方法,以帮助了解神经节苷脂在健康大脑中的空间特异性作用,以及在 CNS 损伤和疾病中的作用。