title: Signaling regulations of neuronal regenerative ability.
abstract: Different from physiological axon growth during development, a major limiting factor for successful axon regeneration is the poor intrinsic regenerative capacity in mature neurons in the adult mammalian central nervous system (CNS). Recent studies identified several molecular pathways, including PTEN/mTOR, Jak/STAT, DLK/JNK, providing important probes in investigating the mechanisms by which the regenerative ability is regulated. This review will summarize these recent findings and speculate their implications.
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; F.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Belin
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: zhigang.he@childrens.harvard.edu.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology* / Q000502:physiology; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D053612:Janus Kinases; D048670:MAP Kinase Kinase 4; D051059:PTEN Phosphohydrolase
references.citation: Nat Commun. 2013;4:2038
references.pmid: 23799397
references.citation: Cell. 2007 Jan 12;128(1):141-56
references.pmid: 17218261
references.citation: J Exp Biol. 1981 Dec;95:231-40
references.pmid: 7334319
references.citation: Neuron. 1994 Jan;12(1):191-204
references.pmid: 7507340
references.citation: J Cell Biol. 2010 Oct 4;191(1):211-23
references.pmid: 20921142
references.citation: Nat Med. 2008 Jan;14(1):69-74
references.pmid: 18157143
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4039-44
references.pmid: 23431164
references.citation: Curr Biol. 2009 Jun 9;19(11):930-6
references.pmid: 19409789
references.citation: Genes Dev. 2012 Jul 15;26(14):1612-25
references.pmid: 22759636
references.citation: Biochem J. 2004 Apr 15;379(Pt 2):301-7
references.pmid: 14711368
references.citation: Cell. 2013 Nov 7;155(4):894-908
references.pmid: 24209626
references.citation: Dev Neurobiol. 2014 Mar;74(3):245-58
references.pmid: 23897628
references.citation: J Neurosci. 2005 Feb 16;25(7):1645-53
references.pmid: 15716400
references.citation: Genes Dev. 2004 Dec 1;18(23):2893-904
references.pmid: 15545625
references.citation: Cell. 2009 Sep 4;138(5):1005-18
references.pmid: 19737525
references.citation: J Comp Neurol. 2003 Mar 10;457(3):293-312
references.pmid: 12541311
references.citation: Cell. 2012 Sep 14;150(6):1264-73
references.pmid: 22980985
references.citation: J Neurosci. 2010 Jul 7;30(27):9306-15
references.pmid: 20610765
references.citation: Nat Cell Biol. 2013 Nov;15(11):1263-5
references.pmid: 24189516
references.citation: J Comp Neurol. 2002 Dec 16;454(3):213-28
references.pmid: 12442313
references.citation: Exp Neurol. 2013 Oct;248:254-7
references.pmid: 23816572
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19587-92
references.pmid: 19875691
references.citation: Nat Commun. 2013;4:2690
references.pmid: 24162165
references.citation: J Neurosci. 2001 Sep 1;21(17):RC164
references.pmid: 11511695
references.citation: PLoS One. 2012;7(9):e44768
references.pmid: 23028614
references.citation: Nat Commun. 2013;4:2633
references.pmid: 24129709
references.citation: Proc Natl Acad Sci U S A. 2012 May 8;109(19):7517-22
references.pmid: 22529377
references.citation: Biochem Soc Trans. 2013 Aug;41(4):906-12
references.pmid: 23863154
references.citation: Ann Neurol. 2011 Jul;70(1):110-20
references.pmid: 21437936
references.citation: Dev Biol. 2007 Dec 15;312(2):596-612
references.pmid: 17949705
references.citation: Annu Rev Cell Dev Biol. 2011;27:441-64
references.pmid: 21985671
references.citation: Prog Brain Res. 2012;201:253-94
references.pmid: 23186719
references.citation: J Neurosci. 2011 Apr 27;31(17):6468-80
references.pmid: 21525288
references.citation: Proc Natl Acad Sci U S A. 2011 May 10;108(19):E99-107
references.pmid: 21518886
references.citation: Exp Neurol. 2008 Feb;209(2):294-301
references.pmid: 17617407
references.citation: Exp Neurol. 2013 Sep;247:653-62
references.pmid: 23510761
references.citation: Invest Ophthalmol Vis Sci. 1999 Mar;40(3):760-6
references.pmid: 10067981
references.citation: EMBO J. 2012 Jun 12;31(14):3063-78
references.pmid: 22692128
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1565-74
references.pmid: 16939975
references.citation: Mol Cell Neurosci. 2012 Jun;50(2):179-92
references.pmid: 22561198
references.citation: Cold Spring Harb Perspect Biol. 2011 Jun 01;3(6):
references.pmid: 21123392
references.citation: J Comp Neurol. 1989 Apr 15;282(3):355-70
references.pmid: 2715387
references.citation: Trends Neurosci. 2006 Nov;29(11):640-6
references.pmid: 17030430
references.citation: Cell Metab. 2012 Apr 4;15(4):505-17
references.pmid: 22482732
references.citation: Genes Dev. 2012 Jul 15;26(14):1509-14
references.pmid: 22802524
references.citation: Neuroscience. 2003;116(3):733-42
references.pmid: 12573715
references.citation: Cancer Cell. 2007 Jul;12(1):9-22
references.pmid: 17613433
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1575-92
references.pmid: 16939976
references.citation: Science. 2011 Feb 18;331(6019):928-31
references.pmid: 21273450
references.citation: Mol Neurobiol. 1996 Aug;13(1):61-79
references.pmid: 8892336
references.citation: Science. 2009 Feb 6;323(5915):802-6
references.pmid: 19164707
references.citation: Science. 1981 Nov 20;214(4523):931-3
references.pmid: 6171034
references.citation: Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3943-54
references.pmid: 11053298
references.citation: Exp Neurol. 2010 Jun;223(2):516-22
references.pmid: 20144891
references.citation: Exp Neurol. 2012 May;235(1):33-42
references.pmid: 21596039
references.citation: Neuron. 2012 Jun 21;74(6):1015-22
references.pmid: 22726832
references.citation: Science. 2009 Oct 9;326(5950):298-301
references.pmid: 19815778
references.citation: J Neurosci. 2009 Nov 11;29(45):14334-41
references.pmid: 19906980
references.citation: Annu Rev Neurosci. 2011;34:131-52
references.pmid: 21438684
references.citation: J Biol Chem. 2010 Sep 3;285(36):28034-43
references.pmid: 20615870
references.citation: Neuron. 2012 Nov 8;76(3):534-48
references.pmid: 23141066
references.citation: J Neurosci. 2000 Jun 15;20(12):4615-26
references.pmid: 10844031
references.citation: Nature. 2011 Nov 06;480(7377):372-5
references.pmid: 22056987
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9149-54
references.pmid: 22615390
references.citation: Nat Neurosci. 2010 Sep;13(9):1075-81
references.pmid: 20694004
references.citation: Cell. 2008 Aug 8;134(3):451-60
references.pmid: 18692468
references.citation: Nat Rev Neurosci. 2012 Feb 15;13(3):183-93
references.pmid: 22334213
references.citation: Physiol Rev. 1996 Apr;76(2):319-70
references.pmid: 8618960
references.citation: Dev Neurobiol. 2011 Dec;71(12):1186-211
references.pmid: 21674813
references.citation: Cytokine Growth Factor Rev. 2008 Oct-Dec;19(5-6):371-81
references.pmid: 18948053
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7109-13
references.pmid: 8041754
references.citation: Cell Death Dis. 2013 Sep 19;4:e805
references.pmid: 24052073
references.citation: J Neurosci. 2009 Jun 3;29(22):7116-23
references.pmid: 19494134
references.citation: Genes Dev. 2011 Sep 15;25(18):1968-81
references.pmid: 21937714
references.citation: Cancer Res. 2000 Dec 15;60(24):7033-8
references.pmid: 11156408
references.citation: Nature. 2007 Nov 29;450(7170):736-40
references.pmid: 18046414
references.citation: Brain. 2007 Dec;130(Pt 12):3308-20
references.pmid: 17971355
references.citation: J Neurosci. 2013 Sep 25;33(39):15350-61
references.pmid: 24068802
references.citation: Biochem Soc Trans. 2013 Aug;41(4):923-6
references.pmid: 23863157
references.citation: J Cell Biol. 2002 Jan 21;156(2):287-97
references.pmid: 11807093
references.citation: Mol Cell Neurosci. 2009 Jul;41(3):313-24
references.pmid: 19394427
references.citation: J Biol Chem. 2005 Mar 18;280(11):9769-72
references.pmid: 15632201
references.citation: J Neurosci. 2010 Nov 17;30(46):15654-63
references.pmid: 21084621
references.citation: Genes Dev. 2004 Dec 1;18(23):2879-92
references.pmid: 15545626
references.citation: Nat Rev Neurosci. 2006 Aug;7(8):603-16
references.pmid: 16858389
references.citation: EMBO J. 2012 Mar 21;31(6):1350-63
references.pmid: 22246183
references.citation: J Neurosci. 2011 Mar 23;31(12):4675-86
references.pmid: 21430166
references.citation: Science. 2012 Jun 1;336(6085):1182-5
references.pmid: 22654062
references.citation: Nat Rev Neurosci. 2006 Aug;7(8):617-27
references.pmid: 16858390
references.citation: J Neurosci. 2013 May 1;33(18):7997-8008
references.pmid: 23637190
references.citation: Eur J Neurosci. 1996 Oct;8(10):2213-20
references.pmid: 8921314
references.citation: Handb Clin Neurol. 2012;109:503-22
references.pmid: 23098733
references.citation: Neuron. 2009 Dec 10;64(5):617-23
references.pmid: 20005819
references.citation: Neuron. 2012 Jun 7;74(5):777-91
references.pmid: 22681683
references.citation: Sci Signal. 2010 Jul 13;3(130):ra53
references.pmid: 20628157
references.citation: Cell Mol Neurobiol. 2001 Dec;21(6):591-604
references.pmid: 12043835
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10738-43
references.pmid: 21670305
references.citation: Cell Rep. 2013 May 30;3(5):1592-606
references.pmid: 23665221
references.citation: J Cell Biol. 2013 Sep 2;202(5):747-63
references.pmid: 23979718
references.citation: FASEB J. 2004 Dec;18(15):1934-6
references.pmid: 15451889