Systems and Cell Biology of Neurodegeneration, IREM, University of Zurich, Schlieren 8952, Switzerland
Systems and Cell Biology of Neurodegeneration, IREM, University of Zurich, Schlieren 8952, Switzerland.
J Neurosci. 2018 Mar 21;38(12):2911-2919. doi: 10.1523/JNEUROSCI.1136-17.2017.
Microglia are emerging as key players in neurodegenerative diseases, such as Alzheimer's disease (AD). Thus far, microglia have rather been known as modulator of neurodegeneration with functions limited to neuroinflammation and release of neurotoxic molecules. However, several recent studies have demonstrated a direct role of microglia in "neuro" degeneration observed in AD by promoting phagocytosis of neuronal, in particular, synaptic structures. While some of the studies address the involvement of the β-amyloid peptides in the process, studies also indicate that this could occur independent of amyloid, further elevating the importance of microglia in AD. Here we review these recent studies and also speculate about the possible cellular mechanisms, and how they could be regulated by risk genes and sleep. Finally, we deliberate on possible avenues for targeting microglia-mediated synapse loss for therapy and prevention..
小胶质细胞在神经退行性疾病中扮演着重要角色，如阿尔茨海默病（AD）。到目前为止，小胶质细胞主要作为神经退行性变的调节剂，其功能仅限于神经炎症和释放神经毒性分子。然而，最近的几项研究表明，小胶质细胞通过促进神经元，特别是突触结构的吞噬作用，直接参与 AD 中观察到的“神经”退化。虽然一些研究涉及β-淀粉样肽在该过程中的作用，但研究也表明，这可能独立于淀粉样蛋白发生，进一步提高了小胶质细胞在 AD 中的重要性。在这里，我们回顾这些最近的研究，并推测可能的细胞机制，以及它们如何被风险基因和睡眠调节。最后，我们讨论了针对小胶质细胞介导的突触丧失的治疗和预防的可能途径。
