Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.
Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.
Ageing Res Rev. 2020 May;59:101039. doi: 10.1016/j.arr.2020.101039. Epub 2020 Feb 24.
Mitochondrial function has long been the focus of many therapeutic strategies for ameliorating age-related neurodegeneration and cognitive decline. Historically, the role of mitochondria in non-neuronal cell types has been overshadowed by neuronal mitochondria, which are responsible for the bulk of oxidative metabolism in the brain. Despite this neuronal bias, mitochondrial function in glial cells, particularly astrocytes, is increasingly recognized to play crucial roles in overall brain metabolism, synaptic transmission, and neuronal protection. Changes in astrocytic mitochondrial function appear to be intimately linked to astrocyte activation/reactivity found in most all age-related neurodegenerative diseases. Here, we address the importance of mitochondrial function to astrocyte signaling and consider how mitochondria could contribute to both the detrimental and protective properties of activated astrocytes. Strategies for protecting astrocytic mitochondrial function, promoting bidirectional transfer of mitochondria between astrocytes and neurons, and transplanting healthy mitochondria to diseased nervous tissue are also discussed.
线粒体功能一直是许多改善与年龄相关的神经退行性变和认知衰退的治疗策略的重点。从历史上看,线粒体在非神经元细胞类型中的作用被神经元线粒体所掩盖,神经元线粒体负责大脑中大部分氧化代谢。尽管存在这种神经元偏向,但胶质细胞(特别是星形胶质细胞)中线粒体的功能越来越被认为在大脑代谢、突触传递和神经元保护中起着至关重要的作用。星形胶质细胞中线粒体功能的变化似乎与大多数与年龄相关的神经退行性疾病中发现的星形胶质细胞激活/反应性密切相关。在这里,我们讨论了线粒体功能对星形胶质细胞信号传递的重要性,并考虑了线粒体如何为激活的星形胶质细胞的有害和保护特性做出贡献。我们还讨论了保护星形胶质细胞线粒体功能、促进星形胶质细胞和神经元之间线粒体的双向转移以及将健康线粒体移植到患病神经组织的策略。