Sabouri Soheila, Rostamirad Marzieh, Dempski Robert E
Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA, United States.
Front Biophys. 2024;2. doi: 10.3389/frbis.2024.1406868. Epub 2024 Jun 11.
Zn transport across neuronal membranes relies on two classes of transition metal transporters: the ZnT (SLC30) and ZIP (SLC39) families. These proteins function to decrease and increase cytosolic Zn levels, respectively. Dysfunction of ZnT and ZIP transporters can alter intracellular Zn levels resulting in deleterious effects. In neurons, imbalances in Zn levels have been implicated as risk factors in conditions such as Alzheimer's disease and neurodegeneration, highlighting the pivotal role of Zn homeostasis in neuropathologies. In addition, Zn modulates the function of plasma membrane proteins, including ion channels and receptors. Changes in Zn levels, on both sides of the plasma membrane, profoundly impact signaling pathways governing cell development, differentiation, and survival. This review is focused on recent developments of neuronal Zn homeostasis, including the impact of Zn dyshomeostasis in neurological disorders, therapeutic approaches, and the increasingly recognized role of Zn as a neurotransmitter in the brain.
锌转运体（SLC30）家族和锌离子转运蛋白（SLC39）家族。这些蛋白质分别起到降低和升高胞质锌水平的作用。锌转运体和锌离子转运蛋白功能失调会改变细胞内锌水平，从而产生有害影响。在神经元中，锌水平失衡被认为是阿尔茨海默病和神经退行性变等病症的风险因素，凸显了锌稳态在神经病理学中的关键作用。此外，锌可调节质膜蛋白的功能，包括离子通道和受体。质膜两侧锌水平的变化会深刻影响控制细胞发育、分化和存活的信号通路。本综述聚焦于神经元锌稳态的最新进展，包括锌稳态失调在神经疾病中的影响、治疗方法，以及锌在大脑中作为神经递质日益被认可的作用。
