Morris Deborah R, Levenson Cathy W
Department of Biomedical Sciences, The Florida State University College of Medicine, Tallahassee, FL, 32306-4300, USA.
Program in Neuroscience, The Florida State University College of Medicine, Tallahassee, FL, 32306-4300, USA.
Adv Neurobiol. 2017;18:303-312. doi: 10.1007/978-3-319-60189-2_15.
Zinc-induced neurotoxicity has been shown to play a role in neuronal damage and death associated with traumatic brain injury, stroke, seizures, and neurodegenerative diseases. During normal firing of "zinc-ergic" neurons, vesicular free zinc is released into the synaptic cleft where it modulates a number of postsynaptic neuronal receptors. However, excess zinc, released after injury or disease, leads to excitotoxic neuronal death. The mechanisms of zinc-mediated neurotoxicity appear to include not only neuronal signaling but also regulation of mitochondrial function and energy production, as well as other mechanisms such as aggregation of amyloid beta peptides in Alzheimer's disease. However, recent data have raised questions about some of our long-standing assumptions about the mechanisms of zinc in neurotoxicity. Thus, this review explores the most recent published findings and highlights the current mechanistic controversies.
锌诱导的神经毒性已被证明在与创伤性脑损伤、中风、癫痫和神经退行性疾病相关的神经元损伤和死亡中起作用。在“锌能”神经元正常放电期间，囊泡游离锌被释放到突触间隙，在那里它调节许多突触后神经元受体。然而，损伤或疾病后释放的过量锌会导致兴奋性毒性神经元死亡。锌介导的神经毒性机制似乎不仅包括神经元信号传导，还包括线粒体功能和能量产生的调节，以及其他机制，如阿尔茨海默病中β淀粉样肽的聚集。然而，最近的数据对我们一些关于锌在神经毒性中的机制的长期假设提出了质疑。因此，本综述探讨了最近发表的研究结果，并突出了当前的机制争议。
