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Role of cytochrome c in α-synuclein radical formation: implications of α-synuclein in neuronal death in Maneb- and paraquat-induced model of Parkinson’s disease

Overview of attention for article published in Molecular Neurodegeneration, November 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (58th percentile)

Mentioned by

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1 news outlet
twitter
1 tweeter

Citations

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16 Dimensions

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35 Mendeley
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Title
Role of cytochrome c in α-synuclein radical formation: implications of α-synuclein in neuronal death in Maneb- and paraquat-induced model of Parkinson’s disease
Published in
Molecular Neurodegeneration, November 2016
DOI 10.1186/s13024-016-0135-y
Pubmed ID
Authors

Ashutosh Kumar, Douglas Ganini, Ronald P. Mason

Abstract

The pathological features of Parkinson's disease (PD) include an abnormal accumulation of α-synuclein in the surviving dopaminergic neurons. Though PD is multifactorial, several epidemiological reports show an increased incidence of PD with co-exposure to pesticides such as Maneb and paraquat (MP). In pesticide-related PD, mitochondrial dysfunction and α-synuclein oligomers have been strongly implicated, but the link between the two has not yet been understood. Similarly, the biological effects of α-synuclein or its radical chemistry in PD is largely unknown. Mitochondrial dysfunction during PD pathogenesis leads to release of cytochrome c in the cytosol. Once in the cytosol, cytochrome c has one of two fates: It either binds to apaf1 and initiates apoptosis or can act as a peroxidase. We hypothesized that as a peroxidase, cytochrome c leaked out from mitochondria can form radicals on α-synuclein and initiate its oligomerization. Samples from controls, and MP co-exposed wild-type and α-synuclein knockout mice were studied using immuno-spin trapping, confocal microscopy, immunohistochemistry, and microarray experiments. Experiments with MP co-exposed mice showed cytochrome c release in cytosol and its co-localization with α-synuclein. Subsequently, we used immuno-spin trapping method to detect the formation of α-synuclein radical in samples from an in vitro reaction mixture consisting of cytochrome c, α-synuclein, and hydrogen peroxide. These experiments indicated that cytochrome c plays a role in α-synuclein radical formation and oligomerization. Experiments with MP co-exposed α-synuclein knockout mice, in which cytochrome c-α synuclein co-localization and interaction cannot occur, mice showed diminished protein radical formation and neuronal death, compared to wild-type MP co-exposed mice. Microarray data from MP co-exposed wild-type and α-synuclein knockout mice further showed that the absence of α-synuclein per se or its co-localization with cytochrome c confers protection from MP co-exposure, as several important pathways were unaffected in α-synuclein knockout mice. Altogether, these results show that peroxidase activity of cytochrome c contributes to α-synuclein radical formation and oligomerization, and that α-synuclein, through its co-localization with cytochrome c or on its own, affects several biological pathways which contribute to increased neuronal death in an MP-induced model of PD.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 8 23%
Student > Ph. D. Student 5 14%
Student > Master 5 14%
Student > Doctoral Student 3 9%
Student > Postgraduate 2 6%
Other 4 11%
Unknown 8 23%
Readers by discipline Count As %
Neuroscience 9 26%
Biochemistry, Genetics and Molecular Biology 6 17%
Chemistry 2 6%
Medicine and Dentistry 2 6%
Psychology 2 6%
Other 4 11%
Unknown 10 29%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 December 2016.
All research outputs
#934,470
of 8,800,428 outputs
Outputs from Molecular Neurodegeneration
#110
of 432 outputs
Outputs of similar age
#45,847
of 303,053 outputs
Outputs of similar age from Molecular Neurodegeneration
#4
of 17 outputs
Altmetric has tracked 8,800,428 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 432 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.3. This one has gotten more attention than average, scoring higher than 70% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 303,053 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.