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Excitatory Dendritic Mitochondrial Calcium Toxicity: Implications for Parkinson’s and Other Neurodegenerative Diseases

Overview of attention for article published in Frontiers in Neuroscience, August 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • Good Attention Score compared to outputs of the same age and source (73rd percentile)

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1 news outlet
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Citations

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63 Dimensions

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162 Mendeley
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Title
Excitatory Dendritic Mitochondrial Calcium Toxicity: Implications for Parkinson’s and Other Neurodegenerative Diseases
Published in
Frontiers in Neuroscience, August 2018
DOI 10.3389/fnins.2018.00523
Pubmed ID
Authors

Manish Verma, Zachary Wills, Charleen T. Chu

Abstract

Dysregulation of calcium homeostasis has been linked to multiple neurological diseases. In addition to excitotoxic neuronal cell death observed following stroke, a growing number of studies implicate excess excitatory neuronal activity in chronic neurodegenerative diseases. Mitochondria function to rapidly sequester large influxes of cytosolic calcium through the activity of the mitochondrial calcium uniporter (MCU) complex, followed by more gradual release via calcium antiporters, such as NCLX. Increased cytosolic calcium levels almost invariably result in increased mitochondrial calcium uptake. While this response may augment mitochondrial respiration, limiting classic excitotoxic injury in the short term, recent studies employing live calcium imaging and molecular manipulation of calcium transporter activities suggest that mitochondrial calcium overload plays a key role in Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and related dementias [PD with dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)]. Herein, we review the literature on increased excitatory input, mitochondrial calcium dysregulation, and the transcriptional or post-translational regulation of mitochondrial calcium transport proteins, with an emphasis on the PD-linked kinases LRRK2 and PINK1. The impact on pathological dendrite remodeling and neuroprotective effects of manipulating MCU, NCLX, and LETM1 are reviewed. We propose that shortening and simplification of the dendritic arbor observed in neurodegenerative diseases occur through a process of excitatory mitochondrial toxicity (EMT), which triggers mitophagy and perisynaptic mitochondrial depletion, mechanisms that are distinct from classic excitotoxicity.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 162 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 162 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 26 16%
Student > Ph. D. Student 25 15%
Student > Master 17 10%
Student > Bachelor 17 10%
Student > Doctoral Student 10 6%
Other 16 10%
Unknown 51 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 27 17%
Neuroscience 27 17%
Agricultural and Biological Sciences 20 12%
Medicine and Dentistry 14 9%
Pharmacology, Toxicology and Pharmaceutical Science 8 5%
Other 13 8%
Unknown 53 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 24 August 2018.
All research outputs
#2,984,709
of 25,385,509 outputs
Outputs from Frontiers in Neuroscience
#1,952
of 11,542 outputs
Outputs of similar age
#56,994
of 341,958 outputs
Outputs of similar age from Frontiers in Neuroscience
#60
of 233 outputs
Altmetric has tracked 25,385,509 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 11,542 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.0. This one has done well, scoring higher than 82% 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 341,958 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 83% of its contemporaries.
We're also able to compare this research output to 233 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 73% of its contemporaries.