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Molecular chaperones and protein folding as therapeutic targets in Parkinson’s disease and other synucleinopathies

Overview of attention for article published in Acta Neuropathologica Communications, December 2013
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Title
Molecular chaperones and protein folding as therapeutic targets in Parkinson’s disease and other synucleinopathies
Published in
Acta Neuropathologica Communications, December 2013
DOI 10.1186/2051-5960-1-79
Pubmed ID
Authors

Darius Ebrahimi-Fakhari, Laiq-Jan Saidi, Lara Wahlster

Abstract

Changes in protein metabolism are key to disease onset and progression in many neurodegenerative diseases. As a prime example, in Parkinson's disease, folding, post-translational modification and recycling of the synaptic protein α-synuclein are clearly altered, leading to a progressive accumulation of pathogenic protein species and the formation of intracellular inclusion bodies. Altered protein folding is one of the first steps of an increasingly understood cascade in which α-synuclein forms complex oligomers and finally distinct protein aggregates, termed Lewy bodies and Lewy neurites. In neurons, an elaborated network of chaperone and co-chaperone proteins is instrumental in mediating protein folding and re-folding. In addition to their direct influence on client proteins, chaperones interact with protein degradation pathways such as the ubiquitin-proteasome-system or autophagy in order to ensure the effective removal of irreversibly misfolded and potentially pathogenic proteins. Because of the vital role of proper protein folding for protein homeostasis, a growing number of studies have evaluated the contribution of chaperone proteins to neurodegeneration. We herein review our current understanding of the involvement of chaperones, co-chaperones and chaperone-mediated autophagy in synucleinopathies with a focus on the Hsp90 and Hsp70 chaperone system. We discuss genetic and pathological studies in Parkinson's disease as well as experimental studies in models of synucleinopathies that explore molecular chaperones and protein degradation pathways as a novel therapeutic target. To this end, we examine the capacity of chaperones to prevent or modulate neurodegeneration and summarize the current progress in models of Parkinson's disease and related neurodegenerative disorders.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 118 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Bangladesh 1 <1%
Netherlands 1 <1%
Australia 1 <1%
India 1 <1%
United Kingdom 1 <1%
Korea, Republic of 1 <1%
United States 1 <1%
Unknown 111 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 29 25%
Researcher 19 16%
Student > Bachelor 18 15%
Student > Master 16 14%
Student > Doctoral Student 7 6%
Other 14 12%
Unknown 15 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 30 25%
Agricultural and Biological Sciences 29 25%
Neuroscience 13 11%
Medicine and Dentistry 8 7%
Chemistry 6 5%
Other 13 11%
Unknown 19 16%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 26 December 2013.
All research outputs
#18,359,382
of 22,738,543 outputs
Outputs from Acta Neuropathologica Communications
#1,226
of 1,368 outputs
Outputs of similar age
#231,761
of 306,795 outputs
Outputs of similar age from Acta Neuropathologica Communications
#19
of 25 outputs
Altmetric has tracked 22,738,543 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,368 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 5th percentile – i.e., 5% of its peers scored the same or lower than it.
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 306,795 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 25 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.