Toxic effects of dopamine metabolism in Parkinson's disease

Hattori, Nobutaka; Wang, Mei; Taka, Hikari; Fujimura, Tsutomu; Yoritaka, Asako; Kubo, Shinichiro; Mochizuki, Hideki

doi:10.1016/s1353-8020(09)70010-0

Cited by 60 publications

(39 citation statements)

References 23 publications

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“…One possible explanation for this sensitivity could be related to the fact that iron accelerates dopamine oxidation, thereby producing reactive oxygen species such as H 2 O 2 which in turn react with Fe 2? ions generating hydroxyl radicals ( Á OH), a more reactive molecule towards proteins, RNA and DNA [53]. However, further studies are needed to specifically evidence deposition of iron and damage of the dopaminergic neurons in Drosophila.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

2009

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Parkinson's disease (PD) is a common progressive neurodegenerative disorder, for which at present no causal treatment is available. On the understanding that the causes of PD are mainly oxidative stress and mitochondrial dysfunction, antioxidants and other drugs are expected to be used. In the present study, we demonstrated for the first time that pure polyphenols such as gallic acid, ferulic acid, caffeic acid, coumaric acid, propyl gallate, epicatechin, epigallocatechin, and epigallocatechin gallate protect, rescue and, most importantly, restore the impaired movement activity (i.e., climbing capability) induced by paraquat in Drosophila melanogaster, a valid model of PD. We also showed for the first time that high concentrations of iron (e.g. 15 mM FeSO(4)) are able to diminish fly survival and movement to a similar extent as (20 mM) paraquat treatment. Moreover, paraquat and iron synergistically affect both survival and locomotor function. Remarkably, propyl gallate and epigallocatechin gallate protected and maintained movement abilities in flies co-treated with paraquat and iron. Our findings indicate that pure polyphenols might be potent neuroprotective agents for the treatment of PD against stressful stimuli.

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Section: Discussionmentioning

confidence: 99%

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

2009

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“…This early dysregulation could contribute to the later demise of the neurons, as dopamine has repeatedly shown to be toxic when it escapes normal regulatory mechanisms [43,44]. In support of this hypothesis, polymorphisms in genes involved in dopamine regulation, such as the vesicular and cytoplasmic dopamine transporters have been associated with changes in PD risk in humans and modulation of toxicity to dopamine neurons in experimental models [45,46], and lack of the vesicular transporter induces a loss of dopaminergic neurons in mice [47].…”

Section: Loss Of Striatal Dopamine Is Preceded By Increased Extracellmentioning

confidence: 95%

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

et al. 2012

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Identification of mutations that cause rare familial forms of Parkinson's disease (PD) and subsequent studies of genetic risk factors for sporadic PD have led to an improved understanding of the pathological mechanisms that may cause nonfamilial PD. In particular, genetic and pathological studies strongly suggest that alpha-synuclein, albeit very rarely mutated in PD patients, plays a critical role in the vast majority of individuals with the sporadic form of the disease. We have extensively characterized a mouse model over-expressing full-length, human, wild-type alpha-synuclein under the Thy-1 promoter. We have also shown that this model reproduces many features of sporadic PD, including progressive changes in dopamine release and striatal content, alphasynuclein pathology, deficits in motor and nonmotor functions that are affected in pre-manifest and manifest phases of PD, inflammation, and biochemical and molecular changes similar to those observed in PD. Preclinical studies have already demonstrated improvement with promising new drugs in this model, which provides an opportunity to test novel neuroprotective strategies during different phases of the disorder using endpoint measures with high power to detect drug effects.

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“…In support of this view, parkin-null mice and Parkinson's disease patients exhibit defects in both antioxidant production and mitochondrial functions (21,(72)(73)(74)(75)(76), important for protection from oxidative stress. In this regard, an attractive explanation for selective loss of dopaminergic neurons is that dopamine me- tabolism is associated with excessive production of reactive oxygen and nitrogen species, which might render such neurons particularly vulnerable if defense mechanisms are compromised (77)(78)(79). Therefore, it is significant that we have linked parkin to a key pathway required for neuronal survival in response to oxidative stress.…”

Section: Relevance To Parkinson's Disease and Potential Clinical Implmentioning

confidence: 99%

Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

Ekholm-Reed

Goldberg

Schlossmacher

et al. 2013

Molecular and Cellular Biology

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Toxic effects of dopamine metabolism in Parkinson's disease

Cited by 60 publications

References 23 publications

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

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