Synaptic Zinc: An Emerging Player in Parkinson’s Disease
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<sup>2+&l...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/9/4724 |
| Summary: | 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<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> in the pathophysiology of PD and discuss its potential mechanisms of actions. Emphasis will be placed on the functional interaction between Zn<sup>2+</sup> and glutamatergic NMDA receptors, the most extensively studied synaptic target of Zn<sup>2+</sup>. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |