Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK.
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London, WC1E 6BT, UK.
Mol Neurodegener. 2021 Apr 6;16(1):22. doi: 10.1186/s13024-021-00436-5.
The central role of the resident innate immune cells of the brain (microglia) in neurodegeneration has become clear over the past few years largely through genome-wide association studies (GWAS), and has rapidly become an active area of research. However, a mechanistic understanding (gene to function) has lagged behind. That is now beginning to change, as exemplified by a number of recent exciting and important reports that provide insight into the function of two key gene products - TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) and PLCγ2 (Phospholipase C gamma2) - in microglia, and their role in neurodegenerative disorders. In this review we explore and discuss these recent advances and the opportunities that they may provide for the development of new therapies.
在过去的几年中，通过全基因组关联研究（GWAS），大脑常驻先天免疫细胞（小胶质细胞）在神经退行性变中的核心作用已经变得非常清楚，并且迅速成为一个活跃的研究领域。然而，其机制理解（从基因到功能）却一直滞后。这种情况现在开始发生改变，许多最近令人兴奋且重要的报告提供了对两个关键基因产物——TREM2（髓样细胞触发受体 2）和 PLCγ2（磷脂酶 C 伽马 2）——在小胶质细胞中的功能及其在神经退行性疾病中的作用的深入了解，就是其中的例证。在这篇综述中，我们探讨并讨论了这些最新进展，以及它们可能为开发新疗法提供的机会。
