Coordination of Necessary and Permissive Signals by PTEN Inhibition for CNS Axon Regeneration.

Frontiers in Neuroscience
Jie ZhangYang Hu

Abstract

In the nearly 10 years since PTEN was identified as a prominent intrinsic inhibitor of CNS axon regeneration, the PTEN negatively regulated PI3K-AKT-mTOR pathway has been intensively explored in diverse models of axon injury and diseases and its mechanism for axon regeneration is becoming clearer. It is therefore timely to summarize current knowledge and discuss future directions of translational regenerative research for neural injury and neurodegenerative diseases. Using mouse optic nerve crush as an in vivo retinal ganglion cell axon injury model, we have conducted an extensive molecular dissection of the PI3K-AKT pathway to illuminate the cross-regulating mechanisms in axon regeneration. AKT is the nodal point that coordinates both positive and negative signals to regulate adult CNS axon regeneration through two parallel pathways, activating mTORC1 and inhibiting GSK3ββ. Activation of mTORC1 or its effector S6K1 alone can only slightly promote axon regeneration, whereas blocking mTORC1 significantly prevent axon regeneration, suggesting the necessary role of mTORC1 in axon regeneration. However, mTORC1/S6K1-mediated feedback inhibition prevents potent AKT activation, which suggests a key permissive signal from an unidentifi...Continue Reading

References

Apr 1, 1996·Physiological Reviews·M E Schwab, D Bartholdi
Aug 9, 2002·Molecular and Cellular Biology·Michael P ScheidJames R Woodgett
Aug 18, 2004·Genes & Development·Nissim Hay, Nahum Sonenberg
Oct 7, 2004·Nature Cell Biology·Estela JacintoMichael N Hall
Feb 17, 2005·Molecular and Cellular Biology·Rachael M EastonMorris J Birnbaum
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Oct 14, 2005·The Journal of Biological Chemistry·Richard C Hresko, Mike Mueckler
Jan 19, 2006·Current Opinion in Neurobiology·Dianna E Willis, Jeffery L Twiss
Jul 22, 2006·Nature Reviews. Neuroscience·Glenn Yiu, Zhigang He
Mar 21, 2007·Genes & Development·Ville Hietakangas, Stephen M Cohen
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Sep 5, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John DillShuxin Li
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·Xiaoju Max Ma, John Blenis
Jan 19, 2010·Experimental Neurology·Kevin K ParkZhigang He
Jul 9, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kimberly J ChristieDouglas W Zochodne
Jul 10, 2010·The Journal of Biological Chemistry·Namiko AbeValeria Cavalli
Jul 31, 2010·Molecular Cell·Katrin DüvelBrendan D Manning
Aug 27, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jessica L NielsonOswald Steward
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Mar 8, 2011·Cell·Vittoria ZinzallaMichael N Hall
Mar 26, 2011·Annals of Neurology·Sang Ryong KimRobert E Burke
May 28, 2011·The Journal of Comparative Neurology·Jessica L NielsonOswald Steward
Dec 2, 2011·Frontiers in Molecular Neuroscience·Yun Tai KimFeng-Quan Zhou
Apr 5, 2012·Nature Reviews. Molecular Cell Biology·Min Sup SongPier Paolo Pandolfi
Apr 14, 2012·Nature Reviews. Neuroscience·Hosung JungChristine E Holt
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Jul 10, 2012·The Journal of Biological Chemistry·Minsheng YuanAlexander A Soukas

❮ Previous
Next ❯

Citations

Mar 21, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Min ChenBing Hu
May 28, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Takayuki KodamaHiroshi Yokozaki
Aug 28, 2019·Communications Biology·Marco LeibingerDietmar Fischer
Sep 26, 2020·Neuroscience Insights·Joachim FuchsGeorge Leondaritis
Jan 12, 2020·Communications Biology·Marco LeibingerDietmar Fischer
Feb 19, 2021·Frontiers in Neuroscience·Pei LiJingjing Jiang
Apr 1, 2021·Journal of Biomedical Nanotechnology·Kai YeJiabo Hu
Jul 3, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Yanqiu JiaWei Jin
Nov 17, 2021·Neural Regeneration Research·Bart Nieuwenhuis, Richard Eva

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.