Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Mol Neurobiol. 2018 Feb;55(2):1183-1192. doi: 10.1007/s12035-016-0375-4. Epub 2017 Jan 19.
Ryanodine receptors (RyRs) are intracellular calcium-release channels found on the endoplasmic reticulum of all cells. All three RyR isoforms, RyR1-3, are expressed in the brain, with RyR2 predominating. RyRs are localized within the soma, axons, dendritic spines, and presynaptic terminals of neurons. RyRs are highly expressed in the cerebellum, hippocampus, olfactory region, basal ganglia, and cerebral cortex. During the physiological processes of development and aging, the intracellular calcium homeostasis is largely regulated by RyRs. In this review, we discussed the potential mechanisms underlying development- and age-related RyR regulation. Dysregulation of RyRs can cause imbalance of intracellular calcium levels, leading to cellular vulnerability, impairment of synaptic neuronal function, and eventually neuronal death. Regulation of RyRs may play an essential role in cellular senescence associated with aging, and thus may be pharmacological targets for slowing down aberrant processes and neurodegenerative diseases such as Alzheimer's disease.
Ryanodine 受体（RyRs）是存在于所有细胞内质网中的细胞内钙释放通道。所有三种 RyR 同工型（RyR1-3）在大脑中表达，其中 RyR2 占主导地位。RyRs 位于神经元的体部、轴突、树突棘和突触前末梢内。RyRs 在小脑、海马体、嗅觉区域、基底神经节和大脑皮层中高度表达。在发育和衰老的生理过程中，RyRs 很大程度上调节细胞内钙稳态。在这篇综述中，我们讨论了与发育和年龄相关的 RyR 调节的潜在机制。RyRs 的失调会导致细胞内钙水平失衡，导致细胞易损性、突触神经元功能障碍，最终导致神经元死亡。RyRs 的调节可能在与衰老相关的细胞衰老中发挥重要作用，因此可能是减缓异常过程和神经退行性疾病（如阿尔茨海默病）的药理学靶点。
