NAD 在大脑衰老和神经退行性疾病中的作用。
NAD in Brain Aging and Neurodegenerative Disorders.
机构信息
Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
出版信息
Cell Metab. 2019 Oct 1;30(4):630-655. doi: 10.1016/j.cmet.2019.09.001.
Abstract
NAD is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD-dependent enzymes are involved in synaptic plasticity and neuronal stress resistance. Here, we review emerging findings that reveal key roles for NAD and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer's, Parkinson's, and Huntington diseases, and amyotrophic lateral sclerosis. Advances in understanding the molecular and cellular mechanisms of NAD-based neuronal resilience will lead to novel approaches for facilitating healthy brain aging and for the treatment of a range of neurological disorders.
摘要
NAD 是一种关键的代谢物，参与细胞生物能量学、基因组稳定性、线粒体动态平衡、适应性应激反应和细胞存活。多种依赖 NAD 的酶参与突触可塑性和神经元应激抗性。在这里，我们综述了新发现，这些发现揭示了 NAD 和相关代谢物在神经元适应广泛的生理应激源以及对抗神经退行性疾病中发生的过程中的关键作用，如阿尔茨海默病、帕金森病和亨廷顿病以及肌萎缩侧索硬化症。对基于 NAD 的神经元弹性的分子和细胞机制的理解的进展将导致促进健康大脑衰老和治疗一系列神经疾病的新方法。
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