title: Targeting calpain in synaptic plasticity.
abstract: BACKGROUND
  Calpains represent a family of neutral, calcium-dependent proteases, which modify the function of their target proteins by partial truncation. These proteases have been implicated in numerous cell functions, including cell division, proliferation, migration, and death. In the CNS, where µ-calpain and m-calpain are the main calpain isoforms, their activation has been linked to synaptic plasticity as well as to neurodegeneration. This review will focus on the role of calpains in synaptic plasticity and discuss the possibility of developing methods to manipulate calpain activity for therapeutic purposes.
  
  
  METHODS
  This review covers the literature showing how calpains are implicated in synaptic plasticity and in a number of conditions associated with learning impairment. The possibility of developing new drugs targeting these enzymes for treating these conditions is discussed.
  
  
  CONCLUSIONS
  As evidence accumulates that calpain activation participates in neurodegeneration and cancer, there is interest in developing therapeutic approaches using direct or indirect calpain inhibition. In particular, a peptide derived from the calpain truncation site of mGluR1α was shown to decrease neurodegeneration following neonatal hypoxia/ischemia. More selective approaches need to be developed to target calpain or some of its substrates for therapeutic indications associated with deregulation of synaptic plasticity.
authors: Western University of Health Sciences, Graduate College of Biomedical Sciences, Basic Medical Sciences, COMP , 309 E 2nd St, Pomona, CA 91766, USA. mbaudry@westernu.edu
authors: Michel
authors: M
authors: Baudry
authors: Maggie M
authors: MM
authors: Chou
authors: Xiaoning
authors: X
authors: Bi
mesh_terms: D000818:Animals; D002154:Calpain / Q000502:physiology*; D003599:Cytoskeleton; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D014176:Protein Biosynthesis; D013569:Synapses / Q000502:physiology*
chemical_list: D002154:Calpain
references: Learn Mem. 1996 Sep-Oct;3(2-3):209-17
references: 10456091
references: J Neurosci. 1994 Mar;14(3 Pt 1):1123-9
references: 7509863
references: Curr Opin Neurobiol. 2004 Jun;14(3):311-7
references: 15194111
references: Cell. 2005 Jan 28;120(2):275-85
references: 15680332
references: J Neurocytol. 1993 Dec;22(12):1060-72
references: 8106880
references: J Pharmacol Exp Ther. 2005 Jul;314(1):16-26
references: 15784649
references: J Biol Chem. 2005 Apr 15;280(15):15229-37
references: 15699033
references: Synapse. 1995 Jan;19(1):37-45
references: 7709342
references: Neuron. 2007 Feb 1;53(3):399-412
references: 17270736
references: Nature. 1987 Jul 30-Aug 5;328(6129):426-9
references: 3614346
references: J Neurochem. 2005 Aug;94(3):651-8
references: 15992386
references: Expert Opin Ther Targets. 2011 Mar;15(3):309-23
references: 21244345
references: J Neurosci. 2004 Dec 8;24(49):11035-45
references: 15590920
references: J Biol Chem. 1997 Aug 1;272(31):19248-52
references: 9235918
references: J Neurobiol. 2005 Jul;64(1):116-31
references: 15883999
references: J Neurosci. 2006 Jul 5;26(27):7143-6
references: 16822969
references: J Neurosci. 1997 Jul 15;17(14):5357-65
references: 9204920
references: J Biol Chem. 1992 Nov 5;267(31):22527-33
references: 1358879
references: Mol Cell Biol. 2006 Jul;26(14):5481-96
references: 16809781
references: J Biol Chem. 2004 Feb 6;279(6):4929-40
references: 14627704
references: J Biol Chem. 1995 Nov 3;270(44):26146-51
references: 7592818
references: Rev Neurosci. 2006;17(6):619-34
references: 17283607
references: J Biochem. 2011 Jul;150(1):23-37
references: 21610046
references: J Neurochem. 1991 May;56(5):1630-8
references: 2013758
references: Mol Biol Cell. 2006 Jan;17(1):239-50
references: 16280362
references: Neuron. 1993 May;10(5):805-14
references: 7684233
references: Brain Res. 1990 Oct 15;530(1):91-5
references: 2271955
references: Neuroscience. 1997 Dec;81(4):1123-35
references: 9330373
references: Int J Biochem Cell Biol. 2002 Dec;34(12):1539-43
references: 12379276
references: Neuropharmacology. 2007 Jan;52(1):12-23
references: 16949110
references: Biochemistry. 1988 Mar 22;27(6):2205-11
references: 2837285
references: Neurobiol Learn Mem. 2008 Mar;89(3):201-11
references: 18054504
references: FEBS J. 2006 Aug;273(15):3415-26
references: 16884487
references: Trends Neurosci. 2005 Jan;28(1):12-9
references: 15626492
references: J Biochem. 2001 Nov;130(5):605-11
references: 11686922
references: J Neurosci. 2009 Jun 24;29(25):8129-42
references: 19553453
references: J Biol Chem. 2006 Mar 31;281(13):8497-510
references: 16461767
references: FEBS Lett. 1993 Jun 1;323(3):229-32
references: 8388808
references: Brain Res. 1997 Mar 28;752(1-2):301-6
references: 9106471
references: J Biol Chem. 1989 Oct 25;264(30):17888-96
references: 2553696
references: J Cell Biol. 1983 Feb;96(2):443-8
references: 6833363
references: J Biol Chem. 2010 Apr 9;285(15):11418-26
references: 20150423
references: Biophys J. 2000 May;78(5):2655-67
references: 10777761
references: J Neurosci. 2003 Dec 17;23(37):11759-69
references: 14684878
references: J Biol Chem. 1989 Jun 15;264(17):10096-103
references: 2542320
references: Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15788-92
references: 15505222
references: J Cell Biol. 1998 May 4;141(3):647-62
references: 9566966
references: J Biol Chem. 2004 Feb 13;279(7):6106-14
references: 14581465
references: Mol Cell Biol. 2004 Mar;24(6):2499-512
references: 14993287
references: J Mol Neurosci. 2002 Aug-Oct;19(1-2):135-41
references: 12212771
references: Neuron. 2002 Jul 3;35(1):121-33
references: 12123613
references: Biochem J. 2004 Sep 15;382(Pt 3):1015-23
references: 15239673
references: Sci Signal. 2008 Jun 10;1(23):tr3
references: 18544749
references: EMBO J. 2007 Jun 20;26(12):2981-90
references: 17541403
references: J Neurochem. 1997 Apr;68(4):1484-94
references: 9084418
references: Prog Neurobiol. 2005 Jun;76(2):99-125
references: 16099088
references: Science. 1995 Mar 17;267(5204):1658-62
references: 7886457
references: Science. 1989 Aug 25;245(4920):862-6
references: 2549638
references: Trends Cell Biol. 2002 Jan;12(1):46-54
references: 11854009
references: BMC Evol Biol. 2012 Sep 29;12:193
references: 23020305
references: Brain Res. 1990 Nov 26;534(1-2):317-20
references: 2073593
references: J Neurosci. 2007 Aug 29;27(35):9278-93
references: 17728442
references: J Neurosci. 2010 Jan 20;30(3):1086-95
references: 20089917
references: J Cell Biol. 2005 Oct 24;171(2):349-59
references: 16230460
references: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2628-32
references: 8464868
references: J Biol Chem. 2006 Nov 17;281(46):35567-75
references: 16982626
references: Curr Opin Neurobiol. 1999 Feb;9(1):105-9
references: 10072368
references: Trends Neurosci. 2002 Apr;25(4):180
references: 11998684
references: Brain Res. 1988 Mar 15;444(1):153-8
references: 2834021
references: Neurochem Res. 1991 Aug;16(8):891-8
references: 1787878
references: Neuroscientist. 2008 Oct;14(5):409-14
references: 18000067
references: Brain. 2012 Aug;135(Pt 8):2428-39
references: 22843411
references: Brain Res Mol Brain Res. 1995 Aug;32(1):25-35
references: 7494460
references: Mol Neurobiol. 2008 Aug;38(1):78-100
references: 18686046
references: Neuroscience. 2011 Mar 31;178:13-20
references: 21256931
references: J Neurosci. 2004 Jun 2;24(22):5151-61
references: 15175384
references: Int J Biochem Cell Biol. 2010 Sep;42(9):1401-7
references: 20541031
references: Brain Res. 1990 Nov 26;534(1-2):201-8
references: 2073582
references: J Biol Chem. 2005 Jun 3;280(22):21588-93
references: 15790561
references: EMBO J. 1999 Dec 15;18(24):6880-9
references: 10601010
references: J Neurochem. 2006 Dec;99(5):1328-37
references: 17064361
references: Neuromolecular Med. 2013 Mar;15(1):74-81
references: 22903378
references: Nat Neurosci. 2006 Jul;9(7):887-95
references: 16732277
references: J Exp Med. 1993 Nov 1;178(5):1693-700
references: 8228816
references: N Engl J Med. 2005 Jun 9;352(23):2413-23
references: 15944426
references: J Cell Sci. 2005 Sep 1;118(Pt 17):3829-38
references: 16129881
references: Neuron. 2004 Sep 30;44(1):59-73
references: 15450160
references: J Neurosci. 2003 May 15;23(10):4081-91
references: 12764095
references: J Neurosci. 2000 Feb 1;20(3):1260-71
references: 10648730
references: Brain Res. 1989 Dec 29;505(2):233-8
references: 2598041
references: Expert Opin Ther Pat. 2011 May;21(5):601-36
references: 21434837
references: Neurobiol Learn Mem. 2005 Nov;84(3):222-7
references: 16150618
references: J Pharmacol Exp Ther. 2002 Mar;300(3):717-23
references: 11861773
references: Mol Neurobiol. 2006 Jun;33(3):215-36
references: 16954597
references: J Biol Chem. 2002 Jul 5;277(27):24435-41
references: 11964413
references: Biochem Biophys Res Commun. 2001 Feb 9;280(5):1333-9
references: 11162675
references: Traffic. 2002 Jul;3(7):452-60
references: 12047553
references: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13445-52
references: 8942955
references: Neurosci Lett. 2000 Jun 2;286(2):149-53
references: 10825658
references: EMBO J. 2009 Feb 4;28(3):248-60
references: 19096364
references: J Histochem Cytochem. 2003 Apr;51(4):411-20
references: 12642619
references: Science. 1988 May 13;240(4854):911-3
references: 2834825
references: Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11175-9
references: 7479960
references: Biochem Soc Symp. 1984;49:149-67
references: 6100833
references: J Neurosci. 2006 Jul 5;26(27):7147-50
references: 16822970
references: Cell. 2007 Mar 23;128(6):1219-29
references: 17382888
references: Trends Neurosci. 2002 Nov;25(11):571-7
references: 12392932
references: Physiol Rev. 1990 Oct;70(4):1029-65
references: 2271059
references: Trends Neurosci. 1998 May;21(5):181-8
references: 9610879
references: Int J Biochem Cell Biol. 2002 Jul;34(7):722-5
references: 11950589
references: Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3362-7
references: 8622942
references: Traffic. 2004 Jul;5(7):514-28
references: 15180828
references: J Neurochem. 1997 Sep;69(3):1006-13
references: 9282922
references: Science. 1984 Jun 8;224(4653):1057-63
references: 6144182
references: Nature. 2008 Nov 20;456(7220):409-12
references: 19020623
references: Brain Res. 2000 Apr 28;863(1-2):143-50
references: 10773202
references: Front Neurosci. 2011 Mar 31;5:44
references: 21503141
references: Learn Mem. 2012 Aug 16;19(9):375-84
references: 22904368
references: Mol Cell Neurosci. 2008 Nov;39(3):314-23
references: 18721885
references: Dev Biol. 2008 Jun 1;318(1):82-91
references: 18423434
references: Neuron. 2003 Oct 9;40(2):347-59
references: 14556713
references: J Cell Biol. 2007 Nov 5;179(3):553-65
references: 17967945
references: Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):467-72
references: 11756682
references: Trends Neurosci. 2000 Jan;23(1):20-6
references: 10631785
references: J Neurobiol. 2000 Aug;44(2):126-44
references: 10934317
references: Nature. 1986 Feb 27-Mar 5;319(6056):774-6
references: 2869411
references: Neuron. 2007 Feb 1;53(3):387-97
references: 17270735
references: Life Sci. 2002 Dec 20;72(4-5):355-61
references: 12467876
references: J Neurosci. 2002 Jun 15;22(12):4842-9
references: 12077181
references: Acta Biochim Pol. 2009;56(2):225-34
references: 19513348
references: Trends Neurosci. 1998 Aug;21(8):339-44
references: 9720601
references: Dev Biol. 2003 Nov 15;263(2):216-30
references: 14597197
references: Eur J Neurosci. 2003 Dec;18(11):3150-2
references: 14656312
references: J Neurosci. 1996 Sep 1;16(17):5324-33
references: 8757245
references: Cell Motil Cytoskeleton. 2008 Sep;65(9):687-707
references: 18615630
references: Biochem Soc Trans. 2006 Aug;34(Pt 4):600-4
references: 16856871
references: J Neurosci. 2000 Jul 1;20(13):RC82
references: 10864976
references: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6386-91
references: 11983920