Camandola Simonetta, Mattson Mark P
Laboratory of Neuroscience, National Institute on Aging, Baltimore, MD, USA
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
EMBO J. 2017 Jun 1;36(11):1474-1492. doi: 10.15252/embj.201695810. Epub 2017 Apr 24.
Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress.
脑细胞通常会对神经回路持续活动以及食物剥夺和体力消耗等环境能量应激源所导致的生物能量挑战做出适应性反应。在细胞水平上，这种适应性反应包括现有突触的“强化”、新突触的形成以及干细胞产生新的神经元。在分子水平上，生物能量挑战会导致转录因子的激活，这些转录因子会诱导蛋白质的表达，从而增强神经元对包括中风、阿尔茨海默病和帕金森病在内的脑部疾病发病机制中所涉及的各种代谢、氧化、兴奋性毒性和蛋白毒性应激的抵抗力。新出现的研究结果表明，包括间歇性生物能量挑战（最显著的是运动和饮食能量限制）的生活方式，可以增加大脑在一生中最佳运作且无疾病的可能性。在此，我们概述了调节大脑能量代谢的细胞和分子机制、这些机制在衰老过程和神经退行性疾病中是如何改变的，以及参与神经元对代谢应激适应途径的干预措施在大脑健康和疾病方面的潜在应用。
