Targeting angiogenin in therapy of amyotropic lateral sclerosis.
BACKGROUND
Missense heterozygous mutations in the coding region of angiogenin (ANG) gene, encoding a 14 kDa angiogenic RNase, were recently found in patients of amyotropic lateral sclerosis (ALS). Functional analyses have shown that these are loss-of-function mutations, implying that angiogenin deficiency is associated with ALS pathogenesis and that increasing ANG expression or angiogenin activity could be a novel approach for ALS therapy.


OBJECTIVE
Review the evidence showing the involvement of angiogenin in motor neuron physiology and function, and provide a rationale for targeting angiogenin in ALS therapy.


METHODS
Review the current understanding of the mechanism of angiogenin action in connection with ALS genetics, pathogenesis and therapy.


CONCLUSIONS
ANG is the first gene whose loss-of-function mutations are associated with ALS pathogenesis. Therapeutic modulation of angiogenin level and activity in the spinal cord, either by systemic delivery of angiogenin protein or through retrograde transport of ANG-encoding viral particles, may be beneficial for ALS patients.
Kishikawa
Hiroko
H
Harvard Medical School, Department of Pathology, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Wu
David
D
Hu
Guo-fu
GF
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D006801:Humans; D012335:RNA, Ribosomal / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
D012335:RNA, Ribosomal; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
Proc Natl Acad Sci U S A. 1989 Mar;86(5):1573-7
2646638
Nat Genet. 2006 Apr;38(4):411-3
16501576
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2920-4
8159680
J Neurosci. 2002 Aug 15;22(16):6920-8
12177190
Brain. 1997 Oct;120 ( Pt 10):1723-37
9365366
Biochemistry. 1989 Sep 5;28(18):7401-8
2479414
Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1217-21
7679494
Neuroreport. 2000 Aug 3;11(11):2507-9
10943712
Neuromuscul Disord. 2008 Jan;18(1):68-70
17703939
J Neurol Sci. 2007 Jul 15;258(1-2):123-7
17462671
Hum Mol Genet. 2008 Jan 1;17(1):130-49
17916583
Ann Neurol. 2003;54 Suppl 5:S20-3
12833364
Expert Rev Mol Med. 2006 May 24;8(11):1-22
16723044
Gene. 2006 May 24;373:116-25
16530354
Amyotroph Lateral Scler. 2008;9(1):4-15
18273714
J Med Genet. 1995 Apr;32(4):290-2
7643359
Neuromuscul Disord. 2006 Nov;16(11):800-4
16952453
Am J Hum Genet. 2003 Aug;73(2):383-9
12830400
Ann Neurol. 1997 Feb;41(2):210-21
9029070
Neurology. 2006 Aug 8;67(3):508-10
16894118
Hum Mol Genet. 1999 Feb;8(2):157-64
9931323
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14519-24
16971483
Lancet Neurol. 2007 Oct;6(10):869-77
17827064
Am J Hum Genet. 2004 Nov;75(5):822-31
15372378
Arch Neurol. 2006 Mar;63(3):345-52
16533961
Ann Neurol. 2004 Oct;56(4):564-7
15389897
Nat Genet. 2003 Aug;34(4):383-94
12847526
Biochemistry. 1992 Dec 15;31(49):12477-85
1281426
Nat Rev Neurosci. 2008 Mar;9(3):169-81
18253131
PLoS One. 2008 Jun 11;3(6):e2450
18545701
Ann Neurol. 2006 Mar;59(3):570-4
16358336
J Neurosci. 2001 Sep 1;21(17):6577-87
11517247
J Neurol. 2005 Jul;252(7):782-8
15789135
Nat Genet. 2008 Jan;40(1):29-31
18084291
J Neurogenet. 2004 Apr-Jun;18(2):429-34
15763997
Nat Neurosci. 2005 Jan;8(1):85-92
15568021
Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1677-81
8127865
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2227-31
2006162
J Neurosci. 2007 Jan 10;27(2):304-7
17215390
Science. 1996 Jan 26;271(5248):515-8
8560268
Neuroreport. 1998 Dec 1;9(17):3967-70
9875737
Biochemistry. 2007 Oct 23;46(42):11810-8
17900154
Proc Natl Acad Sci U S A. 1993 May 1;90(9):3815-9
8483899
Nature. 1993 Mar 4;362(6415):59-62
8446170
J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1186-8
15258228
Am J Hum Genet. 2004 Jun;74(6):1128-35
15106121
J Neurosci. 2005 Nov 9;25(45):10372-5
16280575
Nat Genet. 2008 May;40(5):572-4
18372902
Biochemistry. 2003 Jan 14;42(1):121-8
12515546
Ann Neurol. 2008 Apr;63(4):535-8
18288693
Biochemistry. 1992 Sep 1;31(34):8022-9
1380830
Neurology. 1998 Aug;51(2):583-6
9710040
Biochem Biophys Res Commun. 2002 Jun 7;294(2):287-92
12051708
Proc Natl Acad Sci U S A. 1987 Dec;84(24):8783-7
3122207
Neurobiol Aging. 2009 Aug;30(8):1329-31
18068872
Biochemistry. 1989 Feb 21;28(4):1726-32
2497770
Trends Mol Med. 2006 Aug;12(8):345-7
16843725
Nat Neurosci. 2008 Apr;11(4):420-2
18344992
Nat Neurosci. 2007 May;10(5):608-14
17435754
Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12096-100
7991590
Neurol Res. 2003 Mar;25(2):195-200
12635522
Neurology. 1999 Apr 22;52(7):1427-33
10227630
Hum Mol Genet. 1994 Oct;3(10):1757-61
7849698
Hum Mol Genet. 2007 Jun 15;16(12):1445-53
17468498
Proc Natl Acad Sci U S A. 1988 Aug;85(16):5961-5
2457905
Science. 2008 Mar 21;319(5870):1668-72
18309045
Biochem Biophys Res Commun. 1997 Sep 18;238(2):305-12
9299500
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2915-9
8159679
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2886-91
10694572
J Neurosci. 2000 Apr 1;20(7):2534-42
10729333
Muscle Nerve. 2006 Mar;33(3):302-23
16228969
J Neurol Neurosurg Psychiatry. 1996 Nov;61(5):450-5
8937336
Exp Neurol. 2004 Feb;185(2):232-40
14736504
Biochemistry. 1990 Aug 7;29(31):7297-302
1698454
Biochem Biophys Res Commun. 2001 Sep 14;287(1):305-10
11549292
Neurology. 2003 Dec 23;61(12):1766-73
14694044
Curr Opin Rheumatol. 2003 Nov;15(6):730-6
14569202
Neurology. 2008 Jul 22;71(4):253-9
18184915
J Neurol Sci. 2001 Sep 15;190(1-2):17-20
11574101
Biochem Biophys Res Commun. 1994 Sep 30;203(3):1765-72
7945327
Ann Neurol. 2008 Apr;63(4):538-42
18438952
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2222-6
2006161
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7606-11
9207139
Science. 1999 Dec 24;286(5449):2498-500
10617463
J Cell Biochem. 2000 Jan;76(3):452-62
10649442
J Pharmacol Exp Ther. 1997 Aug;282(2):707-14
9262334
PLoS One. 2007 Nov 21;2(11):e1205
18030339
Neurology. 2004 Nov 23;63(10):1936-8
15557516
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7594-9
18492803
Methods Enzymol. 2001;341:263-73
11582782
Neuron. 1998 Mar;20(3):589-602
9539131
Neurology. 2005 Sep 27;65(6):820-5
16093455
Nat Rev Neurosci. 2006 Sep;7(9):710-23
16924260
N Engl J Med. 1994 Mar 3;330(9):585-91
8302340
Nat Rev Neurosci. 2001 Nov;2(11):806-19
11715057
Nature. 2004 May 27;429(6990):413-7
15164063
Biochemistry. 1985 Sep 24;24(20):5480-6
4074709
Neuron. 2006 Oct 5;52(1):39-59
17015226
Neuron. 2005 Dec 22;48(6):885-96
16364894
Neuroreport. 1996 May 31;7(8):1427-31
8856691
BioDrugs. 2005;19(1):31-7
15691215
Ann Neurol. 1998 Jan;43(1):110-6
9450776
Brain Res. 2007 Jul 9;1157:126-37
17512910
N Engl J Med. 2007 Aug 23;357(8):775-88
17671248
Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):956-72
16503123
J Neurochem. 1985 Dec;45(6):1667-76
3850925
Proc Natl Acad Sci U S A. 1989 Nov;86(21):8427-31
2813401
Phys Med Rehabil Clin N Am. 2008 Aug;19(3):607-17, xi
18625419
Science. 2006 Jun 2;312(5778):1389-92
16741123
Neurobiol Aging. 2008 Feb;29(2):314-6
17113198
Am J Hum Genet. 2003 Aug;73(2):397-403
12858291
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8745-52
16361562
Neuroscience. 1997 May;78(2):351-9
9145792
Biochem Biophys Res Commun. 1993 Dec 15;197(2):682-7
8267604
Biochemistry. 1986 Jun 17;25(12):3527-32
2424496
Nat Neurosci. 2007 May;10(5):615-22
17435755
Neurology. 2005 Sep 27;65(6):934-7
16186539
Am J Hum Genet. 2002 Jan;70(1):251-6
11706389
Biol Cell. 2007 Nov;99(11):649-61
17939777
Cancer Res. 2005 Feb 15;65(4):1352-60
15735021
Neurology. 2006 Sep 12;67(5):771-6
16822964
Hum Mol Genet. 2000 Mar 22;9(5):803-11
10749988
Nature. 2006 Aug 24;442(7105):916-9
16862116
Neurosci Lett. 2007 Jun 13;420(2):128-32
17543992
Nat Genet. 2003 Apr;33(4):455-6
12627231
Science. 1987 Jul 17;237(4812):280-2
2440105
Neurogenetics. 2008 Feb;9(1):33-40
18087731
Ann Neurol. 2007 Dec;62(6):609-17
17886298
Lancet. 1996 May 25;347(9013):1425-31
8676624
Nature. 1998 Jun 18;393(6686):702-5
9641683
Curr Opin Cell Biol. 1995 Jun;7(3):319-24
7662360
JAMA. 2000 Oct 4;284(13):1664-9
11015796
Science. 2003 Aug 8;301(5634):839-42
12907804
Nature. 2006 Aug 24;442(7105):920-4
16862115
Nat Genet. 2001 Jun;28(2):131-8
11381259
Hum Mol Genet. 2003 Nov 1;12(21):2753-64
12966034
Neurogenetics. 1998 Dec;2(1):55-60
9933301
Oncogene. 2005 Jan 13;24(3):445-56
15558023
Neurology. 1997 Dec;49(6):1621-30
9409357
Biochemistry. 1985 Sep 24;24(20):5486-94
2866794
Biochim Biophys Acta. 1993 Oct 6;1202(2):281-6
7691185
Lancet Neurol. 2008 May;7(5):409-16
18396105
Ann Neurol. 2007 May;61(5):427-34
17469116
Nat Genet. 2001 Oct;29(2):160-5
11586297
Neurology. 2007 Mar 27;68(13):1002-7
17389304
Biochem Biophys Res Commun. 2007 Jan 12;352(2):509-13
17125737
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2204-9
9122172
Nature. 2005 Jul 14;436(7048):193-200
16015319
Braz J Med Biol Res. 1999 Dec;32(12):1473-8
10585627
Nat Neurosci. 2008 Mar;11(3):251-3
18246065
Science. 2006 Oct 6;314(5796):130-3
17023659
Nature. 1993 Aug 12;364(6438):584
8350919
Nat Immunol. 2003 Mar;4(3):269-73
12548285