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Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine

Overview of attention for article published in Frontiers in Cellular Neuroscience, October 2016
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Title
Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine
Published in
Frontiers in Cellular Neuroscience, October 2016
DOI 10.3389/fncel.2016.00238
Pubmed ID
Authors

Vincent Law, Sophie Dong, Jesusa L. Rosales, Myung-Yung Jeong, Douglas Zochodne, Ki-Young Lee

Abstract

Peripheral nerve regeneration is a slow process that can be associated with limited outcomes and thus a search for novel and effective therapy for peripheral nerve injury and disease is crucial. Here, we found that roscovitine, a synthetic purine nucleoside analog, enhances neurite outgrowth in neuronal-like PC12 cells. Furthermore, ex vivo analysis of pre-injured adult rat dorsal root ganglion (DRG) neurons showed that roscovitine enhances neurite regrowth in these cells. Likewise, in vivo transected sciatic nerves in rats locally perfused with roscovitine had augmented repopulation of new myelinated axons beyond the transection zone. By mass spectrometry, we found that roscovitine interacts with tubulin and actin. It interacts directly with tubulin and causes a dose-dependent induction of tubulin polymerization as well as enhances Guanosine-5'-triphosphate (GTP)-dependent tubulin polymerization. Conversely, roscovitine interacts indirectly with actin and counteracts the inhibitory effect of cyclin-dependent kinases 5 (Cdk5) on Actin-Related Proteins 2/3 (Arp2/3)-dependent actin polymerization, and thus, causes actin polymerization. Moreover, in the presence of neurotrophic factors such as nerve growth factor (NGF), roscovitine-enhanced neurite outgrowth is mediated by increased activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways. Since microtubule and F-actin dynamics are critical for axonal regrowth, the ability of roscovitine to activate the ERK1/2 and p38 MAPK pathways and support polymerization of tubulin and actin indicate a major role for this purine nucleoside analog in the promotion of axonal regeneration. Together, our findings demonstrate a therapeutic potential for the purine nucleoside analog, roscovitine, in peripheral nerve injury.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 2 15%
Student > Master 2 15%
Professor 1 8%
Student > Doctoral Student 1 8%
Student > Bachelor 1 8%
Other 1 8%
Unknown 5 38%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 31%
Pharmacology, Toxicology and Pharmaceutical Science 2 15%
Neuroscience 2 15%
Medicine and Dentistry 1 8%
Agricultural and Biological Sciences 1 8%
Other 0 0%
Unknown 3 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 28 February 2017.
All research outputs
#13,992,567
of 22,893,031 outputs
Outputs from Frontiers in Cellular Neuroscience
#2,035
of 4,257 outputs
Outputs of similar age
#173,968
of 315,552 outputs
Outputs of similar age from Frontiers in Cellular Neuroscience
#24
of 69 outputs
Altmetric has tracked 22,893,031 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,257 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 49th percentile – i.e., 49% 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 315,552 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 69 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 60% of its contemporaries.