Ghosh Ishan, Liu Celina S, Swardfager Walter, Lanctôt Krista L, Anderson Nicole D
Human Biology Program, University of Toronto, Toronto, ON, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, ON, Canada.
Mol Cell Neurosci. 2021 Dec;117:103683. doi: 10.1016/j.mcn.2021.103683. Epub 2021 Nov 12.
Disruptions to the central excitatory-inhibitory (E/I) balance are thought to be related to aging and underlie a host of neural pathologies, including Alzheimer's disease. Aging may induce an increase in excitatory signaling, causing an E/I imbalance, which has been linked to shorter lifespans in mice, flies, and worms. In humans, extended longevity correlates to greater repression of genes involved in excitatory neurotransmission. The repressor element-1 silencing transcription factor (REST) is a master regulator in neural cells and is believed to be upregulated with senescent stimuli, whereupon it counters hyperexcitability, insulin/insulin-like signaling pathway activity, oxidative stress, and neurodegeneration. This review examines the putative mechanisms that distort the E/I balance with aging and neurodegeneration, and the putative roles of REST in maintaining neuronal homeostasis.
中枢兴奋性-抑制性（E/I）平衡的破坏被认为与衰老有关，并构成包括阿尔茨海默病在内的一系列神经病理学的基础。衰老可能会导致兴奋性信号增加，从而引起E/I失衡，这与小鼠、果蝇和蠕虫的较短寿命有关。在人类中，长寿与参与兴奋性神经传递的基因受到更大程度的抑制相关。阻遏元件1沉默转录因子（REST）是神经细胞中的主要调节因子，据信会随着衰老刺激而上调，从而对抗过度兴奋、胰岛素/胰岛素样信号通路活性、氧化应激和神经退行性变。本综述探讨了随着衰老和神经退行性变而扭曲E/I平衡的假定机制，以及REST在维持神经元稳态中的假定作用。
