Blockade of Rapid Influx of Extracellular Zn2+ into Nigral Dopaminergic Neurons Overcomes Paraquat-Induced Parkinson’s Disease in Rats

Tamano, Haruna; Morioka, Hiroki; Nishio, Ryusuke; Takeuchi, Azusa; Takeda, Atsüshi

doi:10.1007/s12035-018-1398-9

Cited by 23 publications

(7 citation statements)

References 46 publications

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“…Zinc exposure has been identified as an environmental risk factor for PD [31] and post-mortem studies revealed excessive zinc depositions in the substantia nigra (SN) and the striatum of patients with idiopathic PD [13,[32][33][34][35]. In line with these observations, in vitro and in vivo experiments with animal models of PD showed that cytosolic accumulation labile zinc is a hallmark of degenerating dopaminergic neurons [36][37][38][39][40][41][42]. Importantly, treatments with intracellular zinc chelators prevent neurodegeneration caused by many neurotoxins (6-OHDA, MPTP, and paraquat) confirming that cytosolic Zn 2+ accumulation contributes to dopaminergic neuronal loss [43][44][45].…”

Section: Zinc Excess and Parkinson's Diseasementioning

confidence: 85%

“…More recently, Tamano and colleagues showed that increased cytosolic levels of toxic Zn 2+ can also be caused by the influx of extracellular zinc into dopaminergic neurons [ 39 , 40 , 41 ]. In brain slices, both 6-OHDA and paraquat have been found to rapidly increase intracellular Zn 2+ levels only in the SNc.…”

Section: Zinc Dyshomeostasis and Parkinson’s Diseasementioning

confidence: 99%

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Synaptic Zinc: An Emerging Player in Parkinson’s Disease

Sikora

Ouagazzal

2021

IJMS

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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+.

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Section: Zinc Excess and Parkinson's Diseasementioning

confidence: 85%

Section: Zinc Dyshomeostasis and Parkinson’s Diseasementioning

confidence: 99%

Synaptic Zinc: An Emerging Player in Parkinson’s Disease

Sikora

Ouagazzal

2021

IJMS

View full text Add to dashboard Cite

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“…A study by Elenga et al (2018) revealed higher adult mortality (65%) as compared to children (22%) due to difference in ingested amounts. In addition, paraquat is also associated with Parkinson’s disease (Bastias-Candia et al, 2019; Tamano et al, 2019). These studies indicate the severe toxicity of paraquat and its potential damage to mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

Paraquat Degradation From Contaminated Environments: Current Achievements and Perspectives

et al. 2019

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Paraquat herbicide has served over five decades to control annual and perennial weeds. Despite agricultural benefits, its toxicity to terrestrial and aquatic environments raises serious concerns. Paraquat cannot rapidly degrade in the environment and is adsorbed in clay lattices that require urgent environmental remediation. Advanced oxidation processes (AOPs) and bioaugmentation techniques have been developed for this purpose. Among various techniques, bioremediation is a cost-effective and eco-friendly approach for pesticide-polluted soils. Though several paraquat-degrading microorganisms have been isolated and characterized, studies about degradation pathways, related functional enzymes and genes are indispensable. This review encircles paraquat removal from contaminated environments through adsorption, photocatalyst degradation, AOPs and microbial degradation. To provide in-depth knowledge, the potential role of paraquat degrading microorganisms in contaminated environments is described as well.

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“…Zn 2+ chelator reversed these effects, suggesting that AMPAR Ca-Zn mediated Zn 2+ influx and damaged nigral dopamine neurons, leading to PD [ 82 ]. 6-OHDA impaired dopamine neurons in the substantia nigra and striatum by promoting extracellular Zn 2+ to flow into dopamine neurons [ 83 ], while blocking Zn 2+ influx into dopamine neurons inhibited paraquat-induced dopamine neuron loss [ 84 ]. In conclusion, a large influx of extracellular Zn 2+ into dopaminergic neurons promoted the development of PD.…”

Section: Zinc Homeostasis and Neuroinflammatory Diseasesmentioning

confidence: 99%

Zinc Homeostasis: An Emerging Therapeutic Target for Neuroinflammation Related Diseases

et al. 2023

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Zinc is an indispensable trace element in the human body and plays an important role in regulating normal growth and development. Zinc homeostasis in the central nervous system is closely related to the development of neuroinflammation, and synaptic zinc homeostasis disorders affect zinc homeostasis in the brain. Under the condition of synaptic zinc homeostasis, proper zinc supplementation improves the body’s immunity and inhibits neuroinflammation. Synaptic zinc homeostasis disorder in the brain promotes the occurrence and development of neuroinflammation. Cerebral ischemia and hypoxia cause a massive release of synaptic Zn2+ into the synaptic cleft, resulting in neurotoxicity and neuroinflammation. Synaptic zinc homeostasis disorder is a high-risk factor for neurodegenerative diseases. Maintaining cerebral zinc homeostasis suppresses the progression of neuroinflammation-mediated neurodegenerative diseases. This article reviews the relationship between brain zinc homeostasis and neuroinflammation and proposes that maintaining synaptic zinc homeostasis prevents neuroinflammation.

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Blockade of Rapid Influx of Extracellular Zn2+ into Nigral Dopaminergic Neurons Overcomes Paraquat-Induced Parkinson’s Disease in Rats

Cited by 23 publications

References 46 publications

Synaptic Zinc: An Emerging Player in Parkinson’s Disease

Synaptic Zinc: An Emerging Player in Parkinson’s Disease

Paraquat Degradation From Contaminated Environments: Current Achievements and Perspectives

Zinc Homeostasis: An Emerging Therapeutic Target for Neuroinflammation Related Diseases

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