Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, USA.
Antioxid Redox Signal. 2011 Apr 1;14(7):1261-73. doi: 10.1089/ars.2010.3386. Epub 2010 Nov 30.
The calcium ion (Ca(2+)) is the main second messenger that helps to transmit depolarization status and synaptic activity to the biochemical machinery of a neuron. These features make Ca(2+) regulation a critical process in neurons, which have developed extensive and intricate Ca(2+) signaling pathways. High intensity Ca(2+) signaling necessitates high ATP consumption to restore basal (low) intracellular Ca(2+) levels after Ca(2+) influx through plasma membrane receptor and voltage-dependent ion channels. Ca(2+) influx may also lead to increased generation of mitochondrial reactive oxygen species (ROS). Impaired abilities of neurons to maintain cellular energy levels and to suppress ROS may impact Ca(2+) signaling during aging and in neurodegenerative disease processes. This review focuses on mitochondrial and endoplasmic reticulum Ca(2+) homeostasis and how they relate to synaptic Ca(2+) signaling processes, neuronal energy metabolism, and ROS generation. Also, the contribution of altered Ca(2+) signaling to neurodegeneration during aging will be considered. Advances in understanding the molecular regulation of Ca(2+) homeostasis and how it is perturbed in neurological disorders may lead to therapeutic strategies that modulate neuronal Ca(2+) signaling to enhance function and counteract disease processes.
钙离子（Ca(2+)）是主要的第二信使，有助于将去极化状态和突触活动传递到神经元的生化机制中。这些特性使得 Ca(2+)调节成为神经元中的关键过程，神经元已经发展出广泛而复杂的 Ca(2+)信号通路。高强度的 Ca(2+)信号需要大量的 ATP 消耗，以在 Ca(2+)通过质膜受体和电压依赖性离子通道内流后恢复基础（低）细胞内 Ca(2+)水平。Ca(2+)内流也可能导致线粒体活性氧（ROS）的产生增加。神经元维持细胞能量水平和抑制 ROS 的能力受损可能会影响衰老和神经退行性疾病过程中的 Ca(2+)信号。这篇综述重点介绍了线粒体和内质网 Ca(2+)稳态，以及它们与突触 Ca(2+)信号转导、神经元能量代谢和 ROS 生成的关系。此外，还将考虑改变的 Ca(2+)信号在衰老过程中对神经退行性变的贡献。对 Ca(2+)稳态分子调节的理解以及它在神经紊乱中如何受到干扰的进展，可能会导致治疗策略的出现，这些策略可以调节神经元 Ca(2+)信号，以增强功能并对抗疾病过程。
