Issues about the physiological functions of prolyl oligopeptidase based on its discordant spatial association with substrates and inconsistencies among mRNA, protein levels, and enzymatic activity.
Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyses proline-containing peptides shorter than 30 amino acids. POP may be associated with cognitive functions, possibly via the cleavage of neuropeptides. Recent studies have also suggested novel non-hydrolytic and non-catalytic functions for POP. Moreover, POP has also been proposed as a regulator of inositol 1,4,5-triphosphate signaling and several other functions such as cell proliferation and differentiation, as well as signal transduction in the central nervous system, and it is suspected to be involved in pathological conditions such as Parkinson's and Alzheimer's diseases and cancer. POP inhibitors have been developed to restore the depleted neuropeptide levels encountered in aging or in neurodegenerative disorders. These compounds have shown some antiamnesic effects in animal models. However, the mechanisms of these hypothesized actions are still far from clear. Moreover, the physiological role of POP has remained unknown, and a lack of basic studies, including its distribution, is obvious. The aim of this review is to gather information about POP and to propose some novel roles for this enzyme based on its distribution and its discordant spatial association with its best known substrates.
Myöhänen
Timo T
TT
Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland. Timo.Myohanen@uku.fi
García-Horsman
J Arturo
JA
Tenorio-Laranga
Jofre
J
Männistö
Pekka T
PT
D000818:Animals; D001921:Brain / Q000201:enzymology; D002384:Catalysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D009043:Motor Activity; D018377:Neurotransmitter Agents / Q000378:metabolism; D009928:Organ Specificity; D000085822:Prolyl Oligopeptidases; D012333:RNA, Messenger / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013379:Substrate Specificity
D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases
Nat Chem Biol. 2007 Oct;3(10):619-29
17876319
Drug News Perspect. 2007 Jun;20(5):293-305
17878957
J Proteome Res. 2008 Aug;7(8):3447-60
18563927
Neurochem Int. 2005 Sep;47(4):248-59
15985312
Eur J Clin Chem Clin Biochem. 1996 Jan;34(1):17-22
8704029
Biochim Biophys Acta. 1976 Jan 23;422(1):138-58
2300
Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11675-80
9326669
J Pharmacol Exp Ther. 1995 Sep;274(3):1370-8
7562510
Peptides. 2008 Sep;29(9):1472-8
18571285
J Neurochem. 1986 Apr;46(4):1304-7
3512777
Braz J Med Biol Res. 1994 Dec;27(12):2821-30
7550002
Neurosci Res. 2007 Mar;57(3):362-71
17134780
J Biochem. 1994 Mar;115(3):449-53
8056756
Acta Endocrinol (Copenh). 1992 Sep;127(3):262-6
1357903
Neurosci Lett. 1996 Aug 23;214(2-3):151-4
8878106
Insect Biochem Mol Biol. 1997 Apr;27(4):337-43
9134713
Methods Enzymol. 1994;244:188-200
7845207
J Gerontol A Biol Sci Med Sci. 2003 Sep;58(9):B792-7
14528034
Mol Cell Neurosci. 2009 Jul;41(3):373-82
19332125
Regul Pept. 1994 Mar 17;50(3):235-45
8016408
Prog Brain Res. 2007;160:273-84
17499120
J Biol Chem. 1999 Aug 20;274(34):24047-53
10446174
Neuropeptides. 2000 Oct;34(5):272-80
11049731
CNS Drug Rev. 2002 Spring;8(1):31-52
12070525
Eur J Biochem. 1995 Jan 15;227(1-2):277-83
7851396
Learn Mem. 2005 Nov-Dec;12(6):594-600
16287718
Eur J Biochem. 1998 Feb 15;252(1):178-83
9523728
Bipolar Disord. 2004 Apr;6(2):156-61
15005755
Protein Eng Des Sel. 2008 Feb;21(2):83-9
18175776
J Cell Biol. 2000 Jun 26;149(7):1455-72
10871285
Science. 1971 Aug 27;173(3999):827-9
5572174
Nature. 1993 Jan 7;361(6407):31-9
8421494
Brain Res. 2004 Feb 27;999(1):20-8
14746918
Toxicol In Vitro. 2006 Dec;20(8):1446-54
16942854
J Neurochem. 1982 Apr;38(4):1151-4
7038048
Neuroscience. 2004;123(1):5-9
14667436
J Biochem. 1997 Jun;121(6):1176-81
9354394
Pharmacol Biochem Behav. 1997 Mar;56(3):427-34
9077579
Eur J Biochem. 2002 Dec;269(23):5813-20
12444969
Nucleic Acids Res. 2008 Jan;36(Database issue):D320-5
17991683
Am Heart J. 2003 Jul;146(1):9-18
12851603
Clin Chim Acta. 1996 May 30;249(1-2):129-39
8737597
J Pharmacobiodyn. 1987 Dec;10(12):730-5
3330562
J Neurochem. 1995 Jul;65(1):234-40
7540663
J Biochem. 1994 Apr;115(4):724-9
8089089
Neurosci Res. 2007 Feb;57(2):248-58
17141345
FEBS J. 2008 Sep;275(17):4415-27
18657187
Protein Eng Des Sel. 2004 Jun;17(6):527-36
15314210
Endocrinology. 1989 Sep;125(3):1492-7
2503371
Learn Mem. 1998 Sep-Oct;5(4-5):317-30
10454357
Mol Pharmacol. 2009 Jan;75(1):218-26
18927208
Physiol Res. 1992;41(6):475-8
1299333
Prog Neurobiol. 1997 Dec;53(6):627-86
9447616
Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jul;29(6):1029-37
15950352
Eur J Biochem. 2004 Jul;271(13):2705-15
15206935
Brain Res. 1984 Dec 24;324(2):261-70
6085024
Mol Cell Neurosci. 2005 Jun;29(2):155-61
15911340
Chem Pharm Bull (Tokyo). 1985 Jun;33(6):24445-51
3905033
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12880-4
11070096
Biochem Pharmacol. 2003 Jul 15;66(2):179-89
12826261
Gene. 1994 Nov 18;149(2):363-6
7959018
J Biochem. 1998 Mar;123(3):540-5
9538240
Epilepsy Res. 1996 Feb;23(1):37-53
8925802
Brain Res. 1988 Apr 12;446(1):173-7
2453256
Biochem Biophys Res Commun. 1997 Jun 27;235(3):641-5
9207212
J Pharmacol Exp Ther. 1997 Oct;283(1):328-35
9336340
Biochim Biophys Acta. 1997 Dec 5;1343(2):160-86
9434107
Experientia. 1990 Jan 15;46(1):94-7
1688809
Glia. 2008 Apr 15;56(6):675-85
18293395
Anticancer Res. 2008 Sep-Oct;28(5A):2813-7
19035315
Neurosci Lett. 2009 Jan 30;450(2):201-5
19041368
J Pharmacobiodyn. 1982 Sep;5(9):734-40
6185666
Eur J Pharmacol. 1996 Jun 3;305(1-3):31-8
8813528
Brain Res. 1990 Sep 10;527(1):159-62
2282478
Endocrinology. 2004 Jul;145(7):3095-100
15117874
J Neurocytol. 2002 Mar-Jun;31(3-5):299-316
12815249
Neuroscience. 1990;39(1):33-58
1708467
J Neuroendocrinol. 2005 May;17(5):306-13
15869566
Neuroscience. 1982 Mar;7(3):639-45
6175921
J Comp Neurol. 2008 Apr 10;507(5):1694-708
18253937
Biochem Biophys Res Commun. 2004 Mar 26;316(1):78-84
15003514
Clin Chim Acta. 2007 Feb;377(1-2):50-61
17034776
Basic Clin Pharmacol Toxicol. 2007 Feb;100(2):132-8
17244263
Methods Enzymol. 1994;244:19-61
7845208
Endocr Rev. 1999 Oct;20(5):599-648
10529897
Int J Biochem. 1985;17(4):521-4
3891453
J Comp Physiol B. 2005 Aug;175(6):433-44
16044310
J Comp Neurol. 1998 Dec 14;402(2):181-96
9845242
Neurology. 1979 Jan;29(1):96-9
370687
J Neurocytol. 2002 Mar-Jun;31(3-5):277-87
12815247
Am J Physiol. 1990 Dec;259(6 Pt 1):E787-91
1979716
Behav Brain Res. 1995 Jan 23;66(1-2):117-27
7538769
Mol Cell Biochem. 1980 Nov 20;32(3):117-21
7007867
J Neural Transm Suppl. 1987;24:163-74
2445913
Biochim Biophys Acta. 1994 Apr 21;1199(3):279-84
8161566
Pharmacol Biochem Behav. 1998 Feb;59(2):361-8
9476982
J Neurochem. 2003 Mar;84(5):919-29
12603817
Regul Pept. 2001 Sep 15;101(1-3):141-7
11495689
Peptides. 2005 Dec;26(12):2536-46
15996789
Peptides. 2006 Jun;27(6):1561-9
16406204
Int J Biochem Cell Biol. 1996 Apr;28(4):441-9
9026355
Neuroscience. 1979;4(1):1-30
32499
J Biol Chem. 1990 Dec 15;265(35):21448-53
2254307
J Neurochem. 1991 Jan;56(1):113-8
1846169
Neuroscience. 2008 Jun 2;153(4):1177-89
18455882
J Mol Endocrinol. 2003 Apr;30(2):87-97
12683933
J Biochem. 1981 Aug;90(2):325-34
7028730
Cell. 1998 Jul 24;94(2):161-70
9695945
Eur J Pharmacol. 1993 Mar 16;233(1):21-8
8472746
J Mol Biol. 2004 Jul 9;340(3):627-37
15210359
Front Neuroendocrinol. 2002 Oct;23(4):317-41
12381329
J Biol Chem. 1995 Jun 9;270(23):13892-8
7775448
J Comp Neurol. 1994 Sep 8;347(2):249-74
7814667
Int J Biochem Cell Biol. 1998 Jan;30(1):99-114
9597757
Behav Brain Res. 1999 Feb 15;99(1):17-25
10512568
J Neurochem. 1980 Sep;35(3):527-35
6161226
Trends Pharmacol Sci. 2000 Feb;21(2):61-4
10664610
Neurochem Res. 2005 Jun-Jul;30(6-7):695-702
16187206
Regul Pept. 2007 Mar 1;139(1-3):52-8
17123646
J Neurochem. 2005 Aug;94(4):970-9
16092940
Brain Res. 1994 Sep 12;656(2):229-35
7529639
J Comp Neurol. 2004 Mar 29;471(2):128-43
14986307
Mol Cell Biochem. 1991 Jul 24;106(1):15-24
1681421
Lancet Neurol. 2003 Aug;2(8):463-72
12878434
Biochem Med Metab Biol. 1991 Apr;45(2):154-60
1679339
Histochem Cell Biol. 2008 Nov;130(5):993-1003
18618130
Neurochem Int. 2002 Apr;40(4):337-45
11792464
Neuroscience. 2008 Oct 15;156(3):580-5
18718510
Horm Metab Res. 1992 Mar;24(3):110-4
1349555
J Neurophysiol. 2000 Aug;84(2):1093-7
10938331
Neurosci Lett. 1996 Jul 26;213(1):29-32
8844705
Int J Biochem Cell Biol. 2001 Jun;33(6):555-76
11378438
EMBO J. 2003 Jun 16;22(12):3004-14
12805215
Hypertension. 2004 May;43(5):1140-5
15037553
Zoolog Sci. 2002 Jan;19(1):93-102
12025410
Nature. 2002 May 16;417(6886):292-5
12015604
Annu Rev Neurosci. 1992;15:403-42
1575449
Neurochem Res. 2007 Aug;32(8):1365-74
17401647
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4465-70
11904358
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1930-4
11172053
Neuropeptides. 2007 Feb;41(1):1-24
17196652
Bull Exp Biol Med. 2006 Nov;142(5):554-6
17415460
Adv Exp Med Biol. 2006;575:103-8
16700513
Peptides. 1990 Mar-Apr;11(2):375-80
2162536
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14009-14
9391143
Naunyn Schmiedebergs Arch Pharmacol. 1996 Feb;353(3):355-62
8692293