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Aging and disease    2016, Vol. 7 Issue (4) : 479-490     DOI: 10.14336/AD.2016.0111
Review Article |
Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease
Gurses Murat Serdar1,*, Ural Mustafa Numan1, Gulec Mehmet Akif2, Akyol Omer3, Akyol Sumeyya4
1Department of Forensic Medicine, School of Medicine, Uludag University, Bursa, Turkey
2Department of Medical Biochemistry, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey
3Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey
4Department of Medical Biology, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey
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The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals. Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer’s disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.

Keywords matrix metalloproteinases      ADAM      ADAMTS      Alzheimer’s disease      neurodegeneration     
Corresponding Authors: Gurses Murat Serdar   
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These authors had equal contribution and are designated as co-first authors.

Issue Date: 01 August 2016
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Gurses Murat Serdar
Ural Mustafa Numan
Gulec Mehmet Akif
Akyol Omer
Akyol Sumeyya
Cite this article:   
Gurses Murat Serdar,Ural Mustafa Numan,Gulec Mehmet Akif, et al. Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease[J]. Aging and disease, 2016, 7(4): 479-490.
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Figure 1.  Domain structure of ADAMTS proteins (It was adapted from Apte SS [7] and Stanton et al. [11])
Figure 2.  The representation of the effects of ADAMTS on Tau production. Reelin binds to its receptors and activates phosphatidylinositol-3-kinase (PI3K) and protein kinase B (PKB/Akt). It leads a remarkable inhibition in glycogen synthase kinase 3β (GSK3β), which is an enzyme that regulates phosphorylation of the microtubule-stabilizing protein tau. After ADAMTS digest Reelin, depressed reelin level may in turn increase tau phosphorylation at the end of the signaling pathway. (It was adapted from the resources Krstic D [57], Hisanaga A [82], and Yu NN [83]).
[1] Hardy J, Selkoe DJ (2002). The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science, 297: 353-356.
[2] Kuno K, Kanada N, Nakashima E, Fujiki F, Ichimura F, Matsushima K (1997). Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem, 272: 556-562.
[3] Nardi JB, Martos R, Walden KK, Lampe DJ, Robertson HM (1999). Expression of lacunin, a large multidomain extracellular matrix protein, accompanies morphogenesis of epithelial monolayers in Manduca sexta. Insect Biochem Mol Biol, 29: 883-897.
[4] Bork P, Beckmann G (1993). The CUB domain. A widespread module in developmentally regulated proteins. J Mol Biol, 231: 539-545.
[5] Baenziger NL, Brodie GN, Majerus PW (1971). A thrombin-sensitive protein of human platelet membrane. Proc Natl Acad Sci USA, 68: 240-243.
[6] Lawler JW, Slayter HS, Coligan JE (1978). Isolation and characterization of a high molecular weight glycoprotein from human blood platelets. J Biol Chem, 253: 8609-8616.
[7] Apte SS (2009). A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J Biol Chem, 284: 31493-31497.
[8] Porter S, Clark IM, Kevorkian L, Edwards DR (2005). The ADAMTS metalloproteinases. Biochem J, 386: 15-27.
[9] Rawlings ND, O'Brien E, Barrett AJ (2002). MEROPS: the protease database. Nucleic Acids Res, 30: 343-346.
[10] Werb Z (1997). ECM and cell surface proteolysis: regulating cellular ecology. Cell, 91: 439-442.
[11] Stanton H, Melrose J, Little CB, Fosang AJ (2011). Proteoglycan degradation by the ADAMTS family of proteinases. Biochim Biophys Acta, 1812: 1616-1629.
[12] Kosik KS (1993). The molecular and cellular biology of tau. Brain Pathol, 3: 39-43.
[13] Himmler A, Drechsel D, Kirschner MW, Martin DW Jr (1989). Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. Mol Cell Biol, 9: 1381-1388.
[14] Cleveland DW, Hwo SY, Kirschner MW (1977). Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J Mol Biol, 116: 207-225.
[15] Kowall NW, Kosik KS (1987). Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease. Ann Neurol, 22: 639-643.
[16] Lichtenberg B, Mandelkow EM, Hagestedt T, Mandelkow E (1988). Structure and elasticity of microtubule-associated protein tau. Nature, 34: 359-362.
[17] Schneider A, Biernat J, von Bergen M, Mandelkow E, Mandelkow EM (1999). Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry, 38: 3549-3558.
[18] Götz J, Probst A, Spillantini MG, Schäfer T, Jakes R, Bürki K, et al. (1995). Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform. EMBO J, 14: 1304-1313.
[19] Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, (1987). The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 325: 733-736.
[20] Mills J, Reiner PB (1999). Regulation of amyloid precursor protein cleavage. J Neurochem, 72: 443-460.
[21] Younkin SG (1998). The role of A beta 42 in Alzheimer's disease. J Physiol Paris, 92: 289-292.
[22] Nunan J, Small DH (2000). Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett, 483: 6-10.
[23] Huang HC, Jiang ZF (2009). Accumulated amyloid-beta peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer's disease. J Alzheimers Dis, 16: 15-27.
[24] Tanzi RE, Moir RD, Wagner SL (2004). Clearance of Alzheimer's Abeta peptide: the many roads to perdition. Neuron, 43: 605-608.
[25] Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M et al. (2010). Neurotoxicity of Alzheimer's disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio. EMBO J, 29: 3408-3420.
[26] Gandy S (2005). The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease. J Clin Invest, 115: 1121-1129.
[27] Bornstein P (1992). Thrombospondins: structure and regulation of expression. FASEB J, 6: 3290-3299.
[28] Levy GG, Motto DG, Ginsburg D (2005). ADAMTS13 turns 3. Blood, 106: 11-17.
[29] Fosang AJ, Little CB (2008). Drug insight: aggrecanases as therapeutic targets for osteoarthritis. Nat Clin Pract, 4: 420-427.
[30] Tortorella MD, Burn TC, Pratta MA, Abbaszade I, Hollis JM, Liu R et al. (1999). Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Science, 284: 1664-1666.
[31] Tortorella MD, Malfait F, Barve RA, Shieh HS, Malfait AM (2009). A review of the ADAMTS family, pharmaceutical targets of the future. Curr Pharm Des, 15: 2359-2374.
[32] Colige A, Sieron AL, Li SW, Schwarze U, Petty E, Wertelecki W et al. (1999). Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Am J Hum Genet, 65: 308-317.
[33] Jungers KA, Le Goff C, Somerville RP, Apte SS (2005). ADAMTS9 is widely expressed during mouse embryo development. Gene Expr Patterns, 5: 609-617.
[34] Velasco J, Li J, DiPietro L, Stepp MA, Sandy JD, Plaas A (2011). ADAMTS5 deletion blocks murine dermal repair through CD44-mediated aggrecan accumulation and modulation of transforming growth factor β1 (TGFβ1) signaling. J Biol Chem, 286: 26016-26027.
[35] Liu CJ (2009). The role of ADAMTS-7 and ADAMTS-12 in the pathogenesis of arthritis. Nat Clin Pract Rheumatol, 5: 38-45.
[36] Blelloch R, Anna-Arriola SS, Gao D, Li Y, Hodgkin J, Kimble J (1999). The gon-1 gene is required for gonadal morphogenesis in Caenorhabditis elegans. Dev Biol, 216: 382-393.
[37] Furlan M, Robles R, Lammle B (1996). Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood, 87: 4223-4234.
[38] Lancellotti S, De Cristofaro R (2011). Structure and proteolytic properties of ADAMTS13, a metalloprotease involved in the pathogenesis of thrombotic microangiopathies. Prog Mol Biol Transl Sci, 99: 105-144.
[39] Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM et al. (2001). Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature, 413: 488-494.
[40] Zhou W, Inada M, Lee TP, Benten D, Lyubsky S, Bouhassira EE et al. (2005). ADAMTS13 is expressed in hepatic stellate cells. Lab Invest, 85: 780-788.
[41] Sandy JD, Westling J, Kenagy RD, Iruela-Arispe ML, Verscharen C, Rodriguez-Mazaneque JC et al. (2001). Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. J Biol Chem, 276: 13372-13378.
[42] Matthews RT, Gary SC, Zerillo C, Pratta M, Solomon K, Arner EC et al. (2000). Brain-enriched hyaluronan binding (BEHAB)/brevican cleavage in a glioma cell line is mediated by a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family member. J Biol Chem, 275: 22695-22703.
[43] Cua RC, Lau LW, Keough MB, Midha R, Apte SS, Yong VW (2013). Overcoming neurite-inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix. Glia, 61: 972-984.
[44] Haddock G, Cross AK, Plumb J, Surr J, Buttle DJ, Bunning RA et al. (2006). Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter. Mult Scler, 12: 386-396.
[45] Hamel MG, Ajmo JM, Leonardo CC, Zuo F, Sandy JD, Gottschall PE (2008). Multimodal signaling by the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) promotes neurite extension. Exp Neurol, 210: 428-440.
[46] Abali O, Gokce EC, Cemil B, Erdogan B, Yonezawa T, Demircan K (2014). Early induction of ADAMTS 1, 4, 5 and 9 in IL-stimulated mouse astrocytes. Turk Neurosurg, 24: 519-524.
[47] Yamaguchi Y (2000). Lecticans: organizers of the brain extracellular matrix. Cell Mol Life Sci, 57: 276-289.
[48] Galtrey CM, Fawcett JW (2007). The role of chondroitin sulfate proteoglycans in regeneration and plasticity in the central nervous system. Brain Res Rev, 54: 1-18.
[49] Satoh K, Suzuki N, Yokota H (2000). ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) is transcriptionally induced in beta-amyloid treated rat astrocytes. Neurosci Lett, 289: 177-180.
[50] Yuan W, Matthews RT, Sandy JD. Gottschall PE (2002). Association between protease-specific proteolytic cleavage of brevican and synaptic loss in the dentate gyrus of kainate-treated rats. Neuroscience, 114: 1091-1101.
[51] Medina-Flores R, Wang G, Bissel SJ, Murphey-Corb M, Wiley CA (2004). Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection. Neurobiol Dis, 16: 604-616.
[52] Mayer J, Hamel MG, Gottschall PE (2005). Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex. BMC Neurosci, 6: 52.
[53] Miguel RF, Pollak A, Lubec G (2005). Metalloproteinase ADAMTS-1 but not ADAMTS-5 is manifold overexpressed in neurodegenerative disorders as Down syndrome, Alzheimer's and Pick's disease. Brain Res Mol Brain Res, 133: 1-5.
[54] Cross AK, Haddock G, Surr J, Plumb J, Bunning RA, Buttle DJ et al. (2006). Woodroofe MN. Differential expression of ADAMTS-1, -4, -5 and TIMP-3 in rat spinal cord at different stages of acute experimental autoimmune encephalomyelitis. J Autoimmun, 26: 16-23.
[55] Ajmo JM, Eakin AK, Hamel MG, Gottschall PE (2008). Discordant localization of WFA reactivity and brevican/ADAMTS-derived fragment in rodent brain. BMC Neurosci, 9: 14.
[56] Howell MD, Torres-Collado AX, Iruela-Arispe ML, Gottschall PE (2012). Selective decline of synaptic protein levels in the frontal cortex of female mice deficient in the extracellular metalloproteinase ADAMTS1. PLoS One, 7: e47226.
[57] Krstic D, Rodriguez M, Knuesel I (2012). Regulated proteolytic processing of Reelin through interplay of tissue plasminogen activator (tPA), ADAMTS- 4, ADAMTS-5, and their modulators. PLoS One, 7: e47793.
[58] Tauchi R, Imagama S, Natori T, Ohgomori T, Muramoto A, Shinjo R et al. (2012). Matsuyama Y, Ishiguro N, Kadomatsu K. The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury. J Neuroinflammation, 9: 53.
[59] Tauchi R, Imagama S, Ohgomori T, Natori T, Shinjo R, Ishiguro N et al. (2012). ADAMTS-13 is produced by glial cells and upregulated after spinal cord injury. Neurosci Lett, 517: 1-6.
[60] Demircan K, Yonezawa T, Takigawa T, Topcu V, Erdogan S, Ucar F et al. (2013). ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse. Neurosci Lett, 544: 25-30.
[61] Lemarchant S, Pruvost M, Montaner J, Emery E, Vivien D, Kanninen K et al. (2013). ADAMTS proteoglycanases in the physiological and pathological central nervous system. J Neuroinflammation, 10: 133.
[62] Lee HR, Shin HK, Park SY, Kim HY, Lee WS, Rhim BY et al. (2014). Hong KW, Kim CD. Cilostazol suppresses β-amyloid production by activating a disintegrin and metalloproteinase 10 via the upregulation of SIRT1-coupled retinoic acid receptor-β. J Neurosci Res, 92: 1581-1590.
[63] Kojro E, Fahrenholz F (2005). The non-amyloidogenic pathway: structure and function of alpha-secretases. Subcell Biochem, 38: 105-127.
[64] Moss ML, Powell G, Miller MA, Edwards L, Qi B, Sang QX et al. (2011). ADAM9 inhibition increases membrane activity of ADAM10 and controls α-secretase processing of amyloid precursor protein. J Biol Chem, 286: 40443-40451.
[65] Bekris LM, Lutz F, Li G, Galasko DR, Farlow MR, Quinn JF et al. (2012) ADAM10 expression and promoter haplotype in Alzheimer's disease. Neurobiol Aging, 33: 2229.e1-2229.e9.
[66] Hata S, Fujishige S, Araki Y, Kato N, Araseki M, Nishimura M et al. (2009). Alcadein cleavages by amyloid beta-precursor protein (APP) alpha- and gamma-secretases generate small peptides, p3-Alcs, indicating Alzheimer disease-related gamma-secretase dysfunction. J Biol Chem, 284: 36024-36033.
[67] Colciaghi F, Borroni B, Pastorino L, Marcello E, Zimmermann M, Cattabeni F et al. (2002). α -Secretase ADAM 10 as well as APPs is reduced in platelets and CSF of Alzheimer disease patients. Mol Med, 8: 67-74.
[68] Tang K, Hynan LS, Baskin F, Rosenberg RN (2006). Platelet amyloid precursor protein processing: a bio-marker for Alzheimer's disease. J Neurol Sci, 240: 53-58.
[69] Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E et al. (2004). A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest, 113: 1456-1464.
[70] Rosenberg RN, Baskin F, Fosmire JA, Risser R, Adams P, Svetlik D et al. (1997). Altered amyloid protein processing in platelets of patients with Alzheimer disease. Arch Neurol, 54: 139-144.
[71] Anderson JJ, Holtz G, Baskin PP, Wang R, Mazzarelli L, Wagner SL et al. (1999). Menzaghi F. Reduced cerebrospinal fluid levels of alpha-secretase-cleaved amyloid precursor protein in aged rats: correlation with spatial memory deficits. Neuroscience, 93: 1409-1420.
[72] Bernstein HG, Bukowska A, Krell D, Bogerts B, Ansorge S, Lendeckel U (2003). Comparative localization of ADAMs 10 and 15 in human cerebral cortex normal aging, Alzheimer disease and Down syndrome. J Neurocytol, 32: 153-160.
[73] Gatta LB, Albertini A, Ravid R, Finazzi D (2002). Levels of beta-secretase BACE and alpha-secretase ADAM10 mRNAs in Alzheimer hippocampus. Neuroreport, 13: 2031-2033.
[74] Bekris LM, Galloway NM, Millard S, Lockhart D, Li G, Galasko DR et al. (2011). Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP cleavage product levels in Alzheimer's disease. Neurobiol Aging, 32: 556.e13-23.
[75] Clark ME, Kelner GS, Turbeville LA, Boyer A, Arden KC, Maki RA (2001). ADAMTS9, a novel member of the ADAM-TS/metallospondin gene family. Genomics, 67: 343-350.
[76] Pehlivan S, Fedakar R, Eren B, Akyol S, Eren F, Turkmen Inanır N et al. (2015). ADAMTS4, 5, 9, and 15 expressions in the autopsied brain of patients with Alzheimers Disease: a preliminary immünohistochemistry study. J Clin Psychopharmacol (in press). DOI:
doi: 10.5455/bcp.20150706034008
[77] D'Arcangelo G, Miao GG, Chen SC, Soares HD, Morgan JI, Curran T (1995). A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature, 374: 719-723.
[78] Herz J, Chen Y (2006). Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev Neurosci, 7: 850-859.
[79] Rogers JT, Weeber EJ (2008). Reelin and apoE actions on signal transduction, synaptic function and memory formation. Neuron Glia Biol, 4: 259-270.
[80] Kocherhans S, Madhusudan A, Doehner J, Breu KS, Nitsch RM, Fritschy JM et al. (2010). Reduced Reelin expression accelerates amyloid-beta plaque formation and tau pathology in transgenic Alzheimer's disease mice. J Neurosci, 30: 9228-9240.
[81] Botella-Lopez A, Burgaya F, Gavin R, Garcia-Ayllon MS, Gomez-Tortosa E, Pena-Casanova J et al. (2006). Reelin expression and glycosylation patterns are altered in Alzheimer's disease. Proc Natl Acad Sci USA, 103: 5573-5578.
[82] Hisanaga A, Morishita S, Suzuki K, Sasaki K, Koie M, Kohno T et al. (2012). A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) cleaves Reelin in an isoform-dependent manner. FEBS Lett, 586: 3349-3353.
[83] Yu NN, Tan MS, Yu JT, Xie AM, Tan L (2015). The Role of Reelin Signaling in Alzheimer's Disease. Mol Neurobiol. (Epub ahead of print).
[84] Végh MJ, Heldring CM, Kamphuis W, Hijazi S, Timmerman AJ, Li KW et al. (2014). Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer's disease. Acta Neuropathol Commun. 2: 76.
[85] Gottschall PE, Howell MD (2015). ADAMTS expression and function in central nervous system injury and disorders. Matrix Biol. 44-46: 70-6.
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