Abstract
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, Zn2+ also acts as a synaptic transmitter in the brain. In the forebrain, subset of glutamatergic neurons, namely cortical neurons projecting to the striatum, use Zn2+ 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 Zn2+ in the pathophysiology of PD and discuss its potential mechanisms of actions. Emphasis will be placed on the functional interaction between Zn2+ and glutamatergic NMDA receptors, the most extensively studied synaptic target of Zn2+.
Highlights
Zinc is the second most prevalent trace element in the human body after iron and is essential for a wide variety of physiological functions
We found that ZnT3 KO mice are remarkably resistant to locomotor deficits and memory impairment induced by partial 6-OHDA lesions (Figure 3A,B), indicating that synaptically released Zn2+ facilitates expression of behavioral deficits
Acute chelation of extracellular Zn2+ directly in the striatum restored locomotor activity impairment induced by full 6-OHDA lesion (Figure 3C). These findings provide strong evidence for a role of synaptic Zn2+ in the pathophysiology of Parkinson’s disease (PD) and suggest that synaptically released Zn2+ in the striatum may promote behavioral deficits by altering synaptic transmission
Summary
Zinc is the second most prevalent trace element in the human body after iron and is essential for a wide variety of physiological functions. Alterations of intracellular zinc homeostasis are recognized as a key factor in the development of PD. Both deficiency and excess of intracellular zinc levels have been implicated in the development of the disease, though overwhelming evidence favor the later mechanism. It is a key role in a myriad of cellular processes, Zn2+ acts as a synaptic transmitter in the brain and emerging evidence indicates that alterations of vesicular (or synaptic).
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