CNRS, Laboratoire de Neurosciences Cognitives, (UMR 729), Aix Marseille Université, 13331 Marseille, France.
CNRS, Institut des Maladies Neurodégénératives, (UMR 5293), Université de Bordeaux, 33000 Bordeaux, France.
Int J Mol Sci. 2021 Apr 29;22(9):4724. doi: 10.3390/ijms22094724.
Alterations of zinc homeostasis have long been implicated in Parkinson's disease (PD). Zinc plays a complex role as both deficiency and excess of intracellular zinc levels have been incriminated in the pathophysiology of the disease. Besides its role in multiple cellular functions, Zn also acts as a synaptic transmitter in the brain. In the forebrain, subset of glutamatergic neurons, namely cortical neurons projecting to the striatum, use Zn as a messenger alongside glutamate. Overactivation of the cortico-striatal glutamatergic system is a key feature contributing to the development of PD symptoms and dopaminergic neurotoxicity. Here, we will cover recent evidence implicating synaptic Zn in the pathophysiology of PD and discuss its potential mechanisms of actions. Emphasis will be placed on the functional interaction between Zn and glutamatergic NMDA receptors, the most extensively studied synaptic target of Zn.
锌稳态的改变长期以来一直与帕金森病（PD）有关。锌在细胞内锌水平的缺乏和过量在疾病的病理生理学中都有牵连，因此发挥着复杂的作用。除了在多种细胞功能中的作用外，Zn 还在大脑中作为突触递质发挥作用。在前脑，谷氨酸能神经元的亚群，即投射到纹状体的皮质神经元，与谷氨酸一起使用 Zn 作为信使。皮质-纹状体谷氨酸能系统的过度激活是导致 PD 症状和多巴胺能神经毒性发展的关键特征。在这里，我们将介绍最近的证据，这些证据表明突触 Zn 在 PD 的病理生理学中的作用，并讨论其潜在的作用机制。重点将放在 Zn 与谷氨酸 NMDA 受体之间的功能相互作用上，这是 Zn 研究最多的突触靶点。
