PMID- 27799897
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 10
DP  - 2016
TI  - Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell 
      Cycle Inhibitor, Roscovitine.
PG  - 238
LID - 238
AB  - 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.
FAU - Law, Vincent
AU  - Law V
AD  - Department of Cell Biology and Anatomy, Arnie Charbonneau Cancer Institute, 
      Hotchkiss Brain Institute, University of Calgary Calgary, AB, Canada.
FAU - Dong, Sophie
AU  - Dong S
AD  - Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of 
      Calgary Calgary, AB, Canada.
FAU - Rosales, Jesusa L
AU  - Rosales JL
AD  - Department of Biochemistry and Molecular Biology, Snyder Institute for Chronic 
      Diseases, University of Calgary Calgary, AB, Canada.
FAU - Jeong, Myung-Yung
AU  - Jeong MY
AD  - Department of Cogno-Mechatronics Engineering, Pusan National University Pusan, 
      South Korea.
FAU - Zochodne, Douglas
AU  - Zochodne D
AD  - Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of 
      Calgary Calgary, AB, Canada.
FAU - Lee, Ki-Young
AU  - Lee KY
AD  - Department of Cell Biology and Anatomy, Arnie Charbonneau Cancer Institute, 
      Hotchkiss Brain Institute, University of Calgary Calgary, AB, Canada.
LA  - eng
PT  - Journal Article
DEP - 20161017
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC5066473
OTO - NOTNLM
OT  - axon
OT  - cytoskeleton
OT  - injury
OT  - peripheral nerve
OT  - regeneration
EDAT- 2016/11/02 06:00
MHDA- 2016/11/02 06:01
PMCR- 2016/01/01
CRDT- 2016/11/02 06:00
PHST- 2016/07/15 00:00 [received]
PHST- 2016/09/30 00:00 [accepted]
PHST- 2016/11/02 06:00 [pubmed]
PHST- 2016/11/02 06:01 [medline]
PHST- 2016/11/02 06:00 [entrez]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2016.00238 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2016 Oct 17;10:238. doi: 10.3389/fncel.2016.00238. 
      eCollection 2016.