Paraquat as an Environmental Risk Factor in Parkinson’s Disease Accelerates Age-Related Degeneration Via Rapid Influx of Extracellular Zn2+ into Nigral Dopaminergic Neurons

Tamano, Haruna; Nishio, Ryusuke; Morioka, Hiroki; Furuhata, Ryo; Komata, Yuuma; Takeda, Atsüshi

doi:10.1007/s12035-019-01642-5

Cited by 22 publications

(8 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Repeated stimulation was possible (Figure 4B,C). The Ca 2+ increase was blocked by treatment with the TRPM2 inhibitor ACA (20 µM) [15,16,17] applied for 4 h prior to and during the measurement. Cellular response to the positive control (trypsin) was not affected (Figure 4D).…”

Section: Resultsmentioning

confidence: 99%

“…Cell death is the most outstanding and common consequence of TRPM2 channel activation, and has been described in several publications (e.g., [8,13,14]). The exact mechanism of TRPM2 activation by H 2 O 2 is still a subject of ongoing research; however, there are well described inhibitors such as N-(p-Amylcinnamoyl)anthranilic acid (ACA) that are widely being used in studies on TRPM2 [15,16,17].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Role for H2O2 and TRPM2 in the Induction of Cell Death: Studies in KGN Cells

et al. 2019

View full text Add to dashboard Cite

Recent studies showed that KGN cells, derived from a human granulosa cell tumor (GCT), express NADPH oxidase 4 (NOX4), an important source of H2O2. Transient receptor potential melastatin 2 (TRPM2) channel is a Ca2+ permeable cation channel that can be activated by H2O2 and plays an important role in cellular functions. It is also able to promote susceptibility to cell death. We studied expression and functionality of TRPM2 in KGN cells and examined GCT tissue microarrays (TMAs) to explore in vivo relevance. We employed live cell, calcium and mitochondrial imaging, viability assays, fluorescence activated cell sorting (FACS) analysis, Western blotting and immunohistochemistry. We confirmed that KGN cells produce H2O2 and found that they express functional TRPM2. H2O2 increased intracellular Ca2+ levels and N-(p-Amylcinnamoyl)anthranilic acid (ACA), a TRPM2 inhibitor, blocked this action. H2O2 caused mitochondrial fragmentation and apoptotic cell death, which could be attenuated by a scavenger (Trolox). Immunohistochemistry showed parallel expression of NOX4 and TRPM2 in all 73 tumor samples examined. The results suggest that GCTs can be endowed with a system that may convey susceptibility to cell death. If so, induction of oxidative stress may be beneficial in GCT therapy. Our results also imply a therapeutic potential for TRPM2 as a drug target in GCTs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Role for H2O2 and TRPM2 in the Induction of Cell Death: Studies in KGN Cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Paraquat is a highly hazardous quarternary nitrogen herbicide ( Tan et al, 2013 ). Its long-term exposure has been implicated as a risk factor for Parkinson’s disease ( Tamano et al, 2019 ). Paraquat causes modifications in α-synuclein and enhances α-synuclein aggregation ( Rokad et al, 2017 ).…”

Section: Impact Of Environmental Toxicants On Neurodegenerative Disor...mentioning

confidence: 99%

Role of Environmental Toxicants on Neurodegenerative Disorders

Nabi

Tabassum

2022

Front. Toxicol.

View full text Add to dashboard Cite

Neurodegeneration leads to the loss of structural and functioning components of neurons over time. Various studies have related neurodegeneration to a number of degenerative disorders. Neurological repercussions of neurodegeneration can have severe impacts on the physical and mental health of patients. In the recent past, various neurodegenerative ailments such as Alzheimer’s and Parkinson’s illnesses have received global consideration owing to their global occurrence. Environmental attributes have been regarded as the main contributors to neural dysfunction-related disorders. The majority of neurological diseases are mainly related to prenatal and postnatal exposure to industrially produced environmental toxins. Some neurotoxic metals, like lead (Pb), aluminium (Al), Mercury (Hg), manganese (Mn), cadmium (Cd), and arsenic (As), and also pesticides and metal-based nanoparticles, have been implicated in Parkinson’s and Alzheimer’s disease. The contaminants are known for their ability to produce senile or amyloid plaques and neurofibrillary tangles (NFTs), which are the key features of these neurological dysfunctions. Besides, solvent exposure is also a significant contributor to neurological diseases. This study recapitulates the role of environmental neurotoxins on neurodegeneration with special emphasis on major neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

show abstract

“…Glu is the major excitatory neurotransmitter in the mammalian central nervous system (CNS), where it participates in the physiological regulation of different processes. It has been demonstrated that excessive endogenous Glu is related to many chronic and acute neurodegenerative disorders such as epilepsy ( Levite et al, 2020 ), amyotrophic lateral sclerosis ( Mishra et al, 2016 ), cerebral ischemia ( Wang et al, 2013 ), AD ( Park et al, 2019 ), and PD ( Tamano et al, 2019 ). Therefore, Glu excitotoxicity plays an important role in the development of PD.…”

Section: Introductionmentioning

confidence: 99%

Glutamic Acid Transporters: Targets for Neuroprotective Therapies in Parkinson’s Disease

Wang

Yan

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a common neurodegenerative disease in middle-aged and elderly individuals. At present, no effective drug has been developed to treat PD. Although a variety of drugs exist for the symptomatic treatment of PD, they all have strong side effects. Most studies on PD mainly focus on dopaminergic neurons. This review highlights the function of glutamic acid transporters (GLTs), including excitatory amino acid transporters (EAATs) and vesicular glutamate transporters (VGLUTs), during the development of PD. In addition, using bioinformatics, we compared the expression of different types of glutamate transporter genes in the cingulate gyrus of PD patients and healthy controls. More importantly, we suggest that the functional roles of glutamate transporters may prove beneficial in the treatment of PD. In summary, VGLUTs and EAATs may be potential targets in the treatment of PD. VGLUTs and EAATs can be used as clinical drug targets to achieve better efficacy. Through this review article, we hope to enable future researchers to improve the condition of PD patients.

show abstract

Paraquat as an Environmental Risk Factor in Parkinson’s Disease Accelerates Age-Related Degeneration Via Rapid Influx of Extracellular Zn2+ into Nigral Dopaminergic Neurons

Cited by 22 publications

References 52 publications

A Role for H2O2 and TRPM2 in the Induction of Cell Death: Studies in KGN Cells

A Role for H2O2 and TRPM2 in the Induction of Cell Death: Studies in KGN Cells

Role of Environmental Toxicants on Neurodegenerative Disorders

Glutamic Acid Transporters: Targets for Neuroprotective Therapies in Parkinson’s Disease

Contact Info

Product

Resources

About