title: Circulating progranulin as a biomarker for neurodegenerative diseases.
abstract: Progranulin is a growth factor involved in the regulation of multiple processes including tumorigenesis, wound repair, development, and inflammation. The recent discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD), and other neurodegenerative diseases leading to dementia, has brought renewed interest in progranulin and its functions in the central nervous system. GRN null mutations cause protein haploinsufficiency, leading to a significant decrease in progranulin levels that can be detected in plasma, serum and cerebrospinal fluid (CSF) of mutation carriers. The dosage of circulating progranulin sped up the identification of GRN mutations thus favoring genotype-phenotype correlation studies. Researchers demonstrated that, in GRN null mutation carriers, the shortage of progranulin invariably precedes clinical symptoms and thus mutation carriers are "captured" regardless of their disease status. GRN is a particularly appealing gene for drug targeting, in the way that boosting its expression may be beneficial for mutation carriers, preventing or delaying the onset of GRN-related neurodegenerative diseases. Physiological regulation of progranulin expression level is only partially known. Progranulin expression reflects mutation status and, intriguingly, its levels can be modulated by some additional factor (i.e. genetic background; drugs). Thus, factors increasing the production and secretion of progranulin from the normal gene are promising potential therapeutic avenues. In conclusion, peripheral progranulin is a nonintrusive highly accurate biomarker for early identification of mutation carriers and for monitoring future treatments that might boost the level of this protein.
authors: Proteomics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia, Italy.
authors: Roberta
authors: R
authors: Ghidoni
authors: Anna
authors: A
authors: Paterlini
authors: Luisa
authors: L
authors: Benussi
keywords: CSF; GRN; Progranulin; blood; cut-off; dementia; expression; frontotemporal; haploinsufficiency; modulator
references: J Neurol Neurosurg Psychiatry. 2007 Jul;78(7):754-6
references: 17371905
references: J Neurol Neurosurg Psychiatry. 2011 May;82(5):476-86
references: 20971753
references: Neurobiol Dis. 2008 Jul;31(1):41-5
references: 18479928
references: Nature. 2006 Aug 24;442(7105):916-9
references: 16862116
references: J Neurol. 2009 Dec;256(12):2043-51
references: 19618231
references: J Neurol Sci. 2009 Dec 15;287(1-2):291-3
references: 19683260
references: J Alzheimers Dis. 2010;22(4):1123-33
references: 20930269
references: Brain. 2011 Mar;134(Pt 3):808-15
references: 21354975
references: Neuron. 2011 Oct 20;72(2):257-68
references: 21944779
references: J Neurol Neurosurg Psychiatry. 1994 Apr;57(4):416-8
references: 8163988
references: Brain. 2009 Mar;132(Pt 3):583-91
references: 19158106
references: Protein Cell. 2010 Jun;1(6):552-62
references: 21204008
references: Cancer Res. 1999 Jul 1;59(13):3222-9
references: 10397269
references: Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):301
references: 19730171
references: J Neurol Sci. 2011 Jan 15;300(1-2):28-32
references: 21047645
references: Arch Neurol. 2007 Oct;64(10):1436-46
references: 17923627
references: J Clin Invest. 2008 Jul;118(7):2438-47
references: 18568075
references: Am J Hum Genet. 2010 Dec 10;87(6):890-7
references: 21087763
references: Brain. 2011 Sep;134(Pt 9):2456-77
references: 21810890
references: J Biol Chem. 2008 Jan 18;283(3):1744-1753
references: 17984093
references: J Endocrinol. 1998 Aug;158(2):145-51
references: 9771457
references: J Alzheimers Dis. 2011;23(1):7-12
references: 20930271
references: Neurodegener Dis. 2012;9(3):121-7
references: 22123177
references: Neurobiol Aging. 2011 Jun;32(6):1157-8
references: 19632744
references: Neurology. 2008 Oct 14;71(16):1235-9
references: 18768919
references: Biochem Biophys Res Commun. 1992 Oct 15;188(1):57-63
references: 1417868
references: Neurology. 2011 Feb 1;76(5):467-74
references: 21178100
references: J Mol Neurosci. 2011 Nov;45(3):354-8
references: 21863316
references: J Neurochem. 2010 Mar;112(5):1305-15
references: 20028451
references: Arch Neurol. 2011 Apr;68(4):488-97
references: 21482928
references: J Biol Chem. 2011 May 6;286(18):16101-8
references: 21454553
references: Hum Mutat. 2008 Dec;29(12):1373-86
references: 18543312
references: J Biol Chem. 1998 Aug 7;273(32):20078-83
references: 9685348
references: Alzheimer Dis Assoc Disord. 2010 Jul-Sep;24(3):308-9
references: 20798611
references: Neurobiol Aging. 2011 Dec;32(12):2326.e5-16
references: 21820214
references: Am J Pathol. 2010 Jul;177(1):334-45
references: 20489155
references: Neurosci Lett. 2010 Jan 22;469(2):234-6
references: 19963041
references: J Alzheimers Dis. 2013;33(1):69-76
references: 22890101
references: Neurology. 2008 Aug 26;71(9):656-64
references: 18565828
references: J Alzheimers Dis. 2011;27(4):791-7
references: 21891869
references: Lancet Neurol. 2007 Oct;6(10):857-68
references: 17826340
references: Neurology. 1998 Dec;51(6):1546-54
references: 9855500
references: J Alzheimers Dis. 2010;22(3):981-4
references: 20858962
references: Neuron. 2011 Oct 20;72(2):245-56
references: 21944778
references: J Neurosci. 2011 Feb 2;31(5):1885-94
references: 21289198
references: J Alzheimers Dis. 2012;30(1):83-90
references: 22366770
references: Hum Mol Genet. 2006 Oct 15;15(20):2988-3001
references: 16950801
references: J Neurosci. 2011 Aug 3;31(31):11126-32
references: 21813674
references: Alzheimer Dis Assoc Disord. 2011 Apr-Jun;25(2):173-8
references: 20975516
references: J Cell Biol. 2008 Apr 7;181(1):37-41
references: 18378771
references: Neurology. 2008 Jul 22;71(4):253-9
references: 18184915
references: Neurology. 2012 Apr 17;78(16):1245-9
references: 22491866
references: Nat Genet. 2010 Mar;42(3):234-9
references: 20154673
references: Ann Neurol. 2006 Sep;60(3):314-22
references: 16983685
references: J Alzheimers Dis. 2011;24(2):253-9
references: 21258152
references: Neurol Sci. 2013 Jun;34(6):899-903
references: 22797721
references: Neurobiol Aging. 2008 Mar;29(3):427-35
references: 17157414
references: J Biol Chem. 1992 Jun 25;267(18):13073-8
references: 1618805
references: Neurology. 2007 Jul 10;69(2):140-7
references: 17620546
references: Brain. 2008 Mar;131(Pt 3):732-46
references: 18245784
references: J Neuropathol Exp Neurol. 2007 Oct;66(10):892-900
references: 17917583
references: Hum Mutat. 2007 Apr;28(4):416
references: 17345602
references: Am J Hum Genet. 2012 Jun 8;90(6):1102-7
references: 22608501
references: Cell Mol Neurobiol. 2012 Jan;32(1):13-6
references: 21800185
references: J Neuropathol Exp Neurol. 2010 Dec;69(12):1191-200
references: 21107132
references: Neurocase. 2010 Jun;16(3):273-9
references: 20087814
references: Hum Mol Genet. 2008 Dec 1;17(23):3631-42
references: 18723524
references: Brain. 2006 Apr;129(Pt 4):841-52
references: 16495329
references: J Neurochem. 2010 Nov;115(3):735-47
references: 20731760
references: PLoS One. 2011;6(8):e23600
references: 21858182
references: Hum Mutat. 2008 Jan;29(1):53-8
references: 18157829
references: BMC Neurol. 2011 May 10;11:50
references: 21569259
references: Nature. 2006 Aug 24;442(7105):920-4
references: 16862115
references: J Alzheimers Dis. 2012;28(4):759-63
references: 22072213
references: Brain. 2007 May;130(Pt 5):1360-74
references: 17439980
references: Arch Neurol. 2011 May;68(5):581-6
references: 21220649
references: PLoS One. 2010 May 10;5(5):e10551
references: 20479936
references: Neuron. 2010 Nov 18;68(4):654-67
references: 21092856
references: J Alzheimers Dis. 2012;31(3):581-91
references: 22647257
references: Neurobiol Dis. 2009 Mar;33(3):379-85
references: 19101631
references: Neuroscience. 2011 Jun 30;185:106-15
references: 21540081
references: J Alzheimers Dis. 2011;26(3):583-90
references: 21677378
references: Dev Dyn. 2003 Aug;227(4):593-9
references: 12889069
references: Ann Neurol. 2009 May;65(5):603-9
references: 19288468
references: BMC Neurosci. 2009 Oct 27;10:130
references: 19860916
references: Brain Res. 2010 Dec 17;1366:1-8
references: 20888804
references: Arch Neurol. 2010 Feb;67(2):161-70
references: 20142524
references: Neurobiol Aging. 2012 Aug;33(8):1851.e17-9
references: 22502998