alpha 2 macroglobulin


Gene Symbol: alpha 2 macroglobulin
Description: alpha-2-macroglobulin
Alias: A2MD, CPAMD5, FWP007, S863-7, alpha-2-macroglobulin, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5, alpha-2-M
Species: human
Products:     alpha 2 macroglobulin

Top Publications

  1. Kuno K, Terashima Y, Matsushima K. ADAMTS-1 is an active metalloproteinase associated with the extracellular matrix. J Biol Chem. 1999;274:18821-6 pubmed
    ..Consequently, ADAMTS-1 is an active metalloprotease that is associated with the extracellular matrix. This study strongly suggests that ADAMTS-1 may play a role in the inflammatory process through its protease activity. ..
  2. Misra U, Gonzalez Gronow M, Gawdi G, Hart J, Johnson C, Pizzo S. The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction. J Biol Chem. 2002;277:42082-7 pubmed
  3. Jensen P, Humle Jørgensen S, Datta P, Sørensen P. Significantly increased fractions of transformed to total alpha2-macroglobulin concentrations in plasma from patients with multiple sclerosis. Biochim Biophys Acta. 2004;1690:203-7 pubmed
    ..The results suggest an important involvement of alpha2M in regulation of increased proteolytic activity occurring in MS disease. ..
  4. Misra U, Deedwania R, Pizzo S. Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. J Biol Chem. 2005;280:26278-86 pubmed
    ..These studies suggest a mechanism by which alpha2M* enhances the metastatic potential of these cells. ..
  5. Wilson M, Yerbury J, Poon S. Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity. Mol Biosyst. 2008;4:42-52 pubmed
    ..Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. ..
  6. French K, Yerbury J, Wilson M. Protease activation of alpha2-macroglobulin modulates a chaperone-like action with broad specificity. Biochemistry. 2008;47:1176-85 pubmed publisher
  7. Yerbury J, Kumita J, Meehan S, Dobson C, Wilson M. alpha2-Macroglobulin and haptoglobin suppress amyloid formation by interacting with prefibrillar protein species. J Biol Chem. 2009;284:4246-54 pubmed publisher
    ..These findings suggest that both alpha(2)M and Hp are likely to play an important role in controlling the inappropriate aggregation of proteins in the extracellular environment. ..
  8. Borth W. Alpha 2-macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J. 1992;6:3345-53 pubmed
  9. Murata A, Ogawa M, Fujimoto K, Kitahara T, Matsuda Y, Kosaki G. Radioimmunoassay of human pancreatic elastase 1. In vitro interaction of human pancreatic elastase 1 with serum protease inhibitors. Enzyme. 1983;30:29-37 pubmed
    ..Its concentration was significantly increased in patients with acute pancreatitis, and although its concentration varied widely in patients with pancreatic cancer, its average concentration in these patients was significantly elevated. ..

More Information

Publications156 found, 100 shown here

  1. Arai Y, Hosoda F, Kobayashi H, Arai K, Hayashi Y, Kamada N, et al. The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10. Blood. 1997;89:3936-44 pubmed
    ..The predicted NUP98-DDX10 fusion protein may promote leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly. ..
  2. Dolmer K, Huang W, Gettins P. NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin. J Biol Chem. 2000;275:3264-9 pubmed
    ..This specific interaction is consistent with a mode of LRP binding to ligands that uses contributions from more than one domain to generate a wide array of different binding sites, each with overall high affinity. ..
  3. Mocchegiani E, Malavolta M. Zinc dyshomeostasis, ageing and neurodegeneration: implications of A2M and inflammatory gene polymorphisms. J Alzheimers Dis. 2007;12:101-9 pubmed
    ..The role played by MT and A2M is reported in ageing and Alzheimer's disease and on some polymorphisms of A2M and inflammatory genes (cytokines and their receptors) because some of them may be affected by zinc, via MT homeostasis. ..
  4. Mantuano E, Mukandala G, Li X, Campana W, Gonias S. Molecular dissection of the human alpha2-macroglobulin subunit reveals domains with antagonistic activities in cell signaling. J Biol Chem. 2008;283:19904-11 pubmed publisher
  5. Wyatt A, Constantinescu P, Ecroyd H, Dobson C, Wilson M, Kumita J, et al. Protease-activated alpha-2-macroglobulin can inhibit amyloid formation via two distinct mechanisms. FEBS Lett. 2013;587:398-403 pubmed publisher
  6. Wyatt A, Kumita J, Mifsud R, Gooden C, Wilson M, Dobson C. Hypochlorite-induced structural modifications enhance the chaperone activity of human ?2-macroglobulin. Proc Natl Acad Sci U S A. 2014;111:E2081-90 pubmed publisher
    ..Our results support the conclusion that ?2M is a specialized chaperone that prevents the extracellular accumulation of misfolded and potentially pathogenic proteins, particularly during innate immune system activity. ..
  7. Zhao K, Murray E, Murray S. Fibroblastic synoviocytes secrete plasma proteins via α2 -macroglobulins serving as intracellular and extracellular chaperones. J Cell Biochem. 2015;116:2563-76 pubmed publisher
  8. Staubli S, Oertli D, Nebiker C. Laboratory markers predicting severity of acute pancreatitis. Crit Rev Clin Lab Sci. 2015;52:273-83 pubmed publisher
    ..Despite these difficulties, research is still very active in finding new markers to predict the severity of AP. ..
  9. Lövgren K, Christensen K, Majewski W, Østrup O, Skov S, Wiinberg B. Acute Haemarthrosis in the Haemophilia A Rat Generates a Local and Systemic Proinflammatory Response. Thromb Haemost. 2017;117:2092-2104 pubmed publisher
  10. Marynen P, Devriendt K, Van den Berghe H, Cassiman J. A genetic polymorphism in a functional domain of human pregnancy zone protein: the bait region. Genomic structure of the bait domains of human pregnancy zone protein and alpha 2 macroglobulin. FEBS Lett. 1990;262:349-52 pubmed
    Genomic clones containing the exons coding for the bait domain of human pregnancy zone protein and alpha 2 macroglobulin were isolated and fragments containing the bait exons were sequenced...
  11. Hall P, Nelles L, Travis J, Roberts R. Proteolytic cleavage sites on alpha 2-macroglobulin resulting in proteinase binding are different for trypsin and Staphylococcus aureus V-8 proteinase. Biochem Biophys Res Commun. 1981;100:8-16 pubmed
  12. Kovacs D. alpha2-macroglobulin in late-onset Alzheimer's disease. Exp Gerontol. 2000;35:473-9 pubmed
    ..These data support an important role for A2M in AD etiopathology. ..
  13. Ambrus G, Gal P, Kojima M, Szilágyi K, Balczer J, Antal J, et al. Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and -2: a study on recombinant catalytic fragments. J Immunol. 2003;170:1374-82 pubmed
    ..Nevertheless, relative rates of reaction with alpha-2-macroglobulin and C1-inhibitor suggest that alpha-2-macroglobulin may be a significant physiological inhibitor of MASP-1. ..
  14. Bian L, Yang J, Guo T, Duan Y, Qin W, Sun Y, et al. Association study of the A2M and LRP1 Genes with Alzheimer disease in the Han Chinese. Biol Psychiatry. 2005;58:731-7 pubmed
    ..Our results indicate that the CTCG haplotype of LRP1 may reduce the risk of late-onset AD, but A2M is not associated with this disease in the Han Chinese population. ..
  15. Wang X, Huang J, Feng M, Ju Z, Wang C, Yang G, et al. Regulatory mutations in the A2M gene are involved in the mastitis susceptibility in dairy cows. Anim Genet. 2014;45:28-37 pubmed publisher
    ..Our findings provided the molecular basis for A2M transcriptional and post-transcriptional regulations. A close relationship between regulatory mutations and mastitis susceptibility of cows also was established. ..
  16. Niu F, Zhao S, Xu C, Chen L, Ye L, Bi G, et al. Identification and functional analysis of differentially expressed genes related to metastatic osteosarcoma. Asian Pac J Cancer Prev. 2014;15:10797-801 pubmed
    ..The response to hormone stimulus, MAPK signaling pathway and focal adhesion may play important roles in metastatic OS. ..
  17. Brasier A, Zhao Y, Wiktorowicz J, Spratt H, Nascimento E, Cordeiro M, et al. Molecular classification of outcomes from dengue virus -3 infections. J Clin Virol. 2015;64:97-106 pubmed publisher
    ..Early detection of intermediate outcomes of DENV-3 will speed clinical trials evaluating vaccines or drug interventions. ..
  18. Yazzie N, Salazar K, Castillo M. Identification, molecular characterization, and gene expression analysis of a CD109 molecule in the Hawaiian bobtail squid Euprymna scolopes. Fish Shellfish Immunol. 2015;44:342-55 pubmed publisher
  19. Wakle Prabagaran M, Lorca R, Ma X, Stamnes S, Amazu C, Hsiao J, et al. BKCa channel regulates calcium oscillations induced by alpha-2-macroglobulin in human myometrial smooth muscle cells. Proc Natl Acad Sci U S A. 2016;113:E2335-44 pubmed publisher
    ..These data demonstrate that α2M* and LRP1 modulate the BKCachannel in human myometrium and that BKCaand its immunomodulatory interacting partners regulate Ca(2+)dynamics in hMSMCs during pregnancy. ..
  20. Suman S, Basak T, Gupta P, Mishra S, Kumar V, Sengupta S, et al. Quantitative proteomics revealed novel proteins associated with molecular subtypes of breast cancer. J Proteomics. 2016;148:183-93 pubmed publisher
    ..Hence, these proteins could have clinical importance for the diagnosis and prognosis purposes among molecular BC subtypes. ..
  21. Cheong S, Hentschel L, Davidson A, Gerrelli D, Davie R, Rizzo R, et al. Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis. Am J Hum Genet. 2016;99:1338-1352 pubmed publisher
    ..Our study delineates a unique form of recessive ASD and defines a role for CPAMD8, a protein of unknown function, in anterior segment development, implying another pathway for the pathogenicity of ASD. ..
  22. Xue Z, Wang L, Liu Z, Wang W, Liu C, Song X, et al. The fragmentation mechanism and immune-protective effect of CfTEP in the scallop Chlamys farreri. Dev Comp Immunol. 2017;76:220-228 pubmed publisher
    ..All these results suggested that CfTEP protein existed as fragments similar to vertebrate C3, and played central roles in the immune response against pathogen in the innate immunity of scallops. ..
  23. Styczynska M, Wasiak B, Łuczywek E, Pfeffer A, Barcikowska M. [Alpha2-macroglobulin gene polymorphism in patients with Alzheimer's disease]. Neurol Neurochir Pol. 2001;35:1013-20 pubmed
    Recent studies suggest that alpha 2-macroglobulin (alpha 2 m) may play a role in the pathogenesis of Alzheimer's Disease (AD). The presence of alpha 2-macroglobulin G/G genotype is thought to increase the risk of AD...
  24. Cacabelos R. Genomic characterization of Alzheimer's disease and genotype-related phenotypic analysis of biological markers in dementia. Pharmacogenomics. 2004;5:1049-105 pubmed
    ..All these genotypic and phenotypic variations bring about important consequences for the pharmacogenomics of AD. ..
  25. Takada T, Kodera Y, Matsubara M, Kawashima Y, Maeda T, Fujita Y, et al. Serum monomeric ?2-macroglobulin as a clinical biomarker in diabetes. Atherosclerosis. 2013;228:270-6 pubmed publisher
    ..It is identical to the human 'cardiac isoform of ?2-macroglobulin' described in the literature, a well-known acute phase serum biomarker protein mechanistically involved in cardiac and atherosclerotic diseases. ..
  26. Mikolajczyk S, Millar L, Kumar A, Saedi M. Human glandular kallikrein, hK2, shows arginine-restricted specificity and forms complexes with plasma protease inhibitors. Prostate. 1998;34:44-50 pubmed
    ..hK2 also formed a rapid complex with alpha 2-macroglobulin. These results demonstrate that hK2 is an active protease with arginine-selective specificity, which forms covalent complexes with plasma protease inhibitors. ..
  27. Zapico I, Coto E, Rodriguez A, Alvarez C, Torre J, Alvarez V. A DNA polymorphism at the alpha2-macroglobulin gene is associated with the severity of rheumatoid arthritis. J Rheumatol. 2000;27:2308-11 pubmed
    ..Carriers of the alpha2m deletion allele would have increased risk of developing an early active severe form of the disease. Our data suggest that alpha2m could be a valuable target in the treatment of RA. ..
  28. Jhoo J, Kim K, Lee D, Lee K, Lee J, Kim S, et al. Association of alpha-2-macroglobulin deletion polymorphism with sporadic Alzheimer's disease in Koreans. J Neurol Sci. 2001;184:21-5 pubmed
    ..015). In conclusion, our data suggests that the A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative subjects. ..
  29. Petersen P, Lei X, Seldin M, Rodriguez S, Byerly M, Wolfe A, et al. Dynamic and extensive metabolic state-dependent regulation of cytokine expression and circulating levels. Am J Physiol Regul Integr Comp Physiol. 2014;307:R1458-70 pubmed publisher
  30. Nartikova V, Paskhina T. [Uniform method for determining the alpha 1-antitrypsin and alpha 2-macroglobulin activity in human blood serum (plasma)]. Vopr Med Khim. 1979;25:494-9 pubmed
    ..1 ml) very rapidly and specifically using commercially available substrate; the method might be recommended for routine clinical analysis. ..
  31. Chen Y, Xu K, Li J, Wang X, Ye Y, Qi P. Molecular characterization of complement component 3 (C3) in Mytilus coruscus improves our understanding of bivalve complement system. Fish Shellfish Immunol. 2018;76:41-47 pubmed publisher
    ..Taken together, these results show that C3 may play an essential role in the immune defense of M. coruscus. The present data therefore provide a more detailed insight into the functional activities of the bivalve complement system. ..
  32. Nachman R, Harpel P. Platelet alpha2-macroglobulin and alpha1-antitrypsin. J Biol Chem. 1976;251:4512-21 pubmed
    ..Platelet protease inhibitors may modulate the protease-mediated events involved in the formation of hemostatic plugs and thrombi. ..
  33. Arnold J, Wallis R, Willis A, Harvey D, Royle L, Dwek R, et al. Interaction of mannan binding lectin with alpha2 macroglobulin via exposed oligomannose glycans: a conserved feature of the thiol ester protein family?. J Biol Chem. 2006;281:6955-63 pubmed
    ..Binding would lead to opsonization or activation of enzyme systems such as complement. ..
  34. Seriramalu R, Pang W, Jayapalan J, Mohamed E, Abdul Rahman P, Bustam A, et al. Application of champedak mannose-binding lectin in the glycoproteomic profiling of serum samples unmasks reduced expression of alpha-2 macroglobulin and complement factor B in patients with nasopharyngeal carcinoma. Electrophoresis. 2010;31:2388-95 pubmed publisher
    ..Together with other acute-phase response proteins that were previously reported to be altered in expression in NPC patients, AMG and CFB may serve as useful complementary biomarkers for NPC. ..
  35. Choi G, Kim J, Shin Y, Ye Y, Kim S, Park H. Eosinophil activation and novel mediators in the aspirin-induced nasal response in AERD. Clin Exp Allergy. 2013;43:730-40 pubmed publisher
    ..Eosinophil activation occurred in early and late responses after L-ASA NPT in upper airway mucosa of AERD patients, where ApoA1, ?2M and CP as well as CysLT may be involved in eosinophilic inflammation. ..
  36. Kelly B, Lautenbach E, Nachamkin I, Coffin S, Gerber J, Fuchs B, et al. Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis. Diagn Microbiol Infect Dis. 2016;85:109-15 pubmed publisher
    ..The combination of A2M and PCT discriminated bacterial sepsis from other SIRS among SICU patients with suspected sepsis. ..
  37. Zhao K, Murray E, Murray S. HK2 Proximal Tubule Epithelial Cells Synthesize and Secrete Plasma Proteins Predominantly Through the Apical Surface. J Cell Biochem. 2017;118:924-933 pubmed publisher
    ..J. Cell. Biochem. 118: 924-933, 2017. © 2016 Wiley Periodicals, Inc. ..
  38. Mortensen S, Sottrup Jensen L, Hansen H, Petersen T, Magnusson S. Primary and secondary cleavage sites in the bait region of alpha 2-macroglobulin. FEBS Lett. 1981;135:295-300 pubmed
  39. Sottrup Jensen L, Stepanik T, Kristensen T, Wierzbicki D, Jones C, Lønblad P, et al. Primary structure of human alpha 2-macroglobulin. V. The complete structure. J Biol Chem. 1984;259:8318-27 pubmed
    ..The properties of alpha 2-macroglobulin are discussed within the context of proteolytically regulated systems with particular reference to the complement components C3 and C4. ..
  40. McElhinney B, Ardill J, Caldwell C, Lloyd F, McClure N. Ovarian hyperstimulation syndrome and assisted reproductive technologies: why some and not others?. Hum Reprod. 2002;17:1548-53 pubmed
    ..alpha(2)M measurements may help to differentiate those for whom it is safe to proceed with embryo transfer from those for whom it is not, because of the risk of OHSS. ..
  41. Arandjelovic S, Hall B, Gonias S. Mutation of lysine 1370 in full-length human alpha2-macroglobulin blocks binding to the low density lipoprotein receptor-related protein-1. Arch Biochem Biophys. 2005;438:29-35 pubmed
    ..7 cells was blocked by receptor-associated protein, indicating an essential role for LRP-1. These studies demonstrate that a single mutation in full-length r(alpha)2M is sufficient to block binding to LRP-1. ..
  42. Domingues Montanari S, Hernandez Guillamon M, Fernandez Cadenas I, Mendioroz M, Boada M, Munuera J, et al. ACE variants and risk of intracerebral hemorrhage recurrence in amyloid angiopathy. Neurobiol Aging. 2011;32:551.e13-22 pubmed publisher
    ..012). These results suggest that variants in the ACE are associated with CAA-related ICH recurrence, possibly by modulating ACE protein level. ..
  43. Narita K, Sasamoto S, Koizumi S, Okazaki S, Nakamura H, Inoue T, et al. TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. FASEB J. 2015;29:2247-59 pubmed publisher
    ..Overall, this study demonstrated a novel physiologic function of TRPV4 in the regulation of BCSFB permeability. ..
  44. Ferrier G, Kim S, Kaddis C, Loo J, Ann Zimmer C, Zimmer R. MULTIFUNCin: A Multifunctional Protein Cue Induces Habitat Selection by, and Predation on, Barnacles. Integr Comp Biol. 2016;56:901-913 pubmed
    ..As a multifunctional protein cue, MULTIFUNCin provides valuable sensory information, conveys different messages to different species, and drives complex biotic interactions. ..
  45. Bísaro de Lorenc L, Ramos A, Sanchez M, Montenegro R, Chiabrando G. Structural evaluation of plasma alpha2-macroglobulin in acute pancreatitis. Clin Chem Lab Med. 2005;43:1183-9 pubmed
    ..Finally, the structural evaluation of plasma alpha2-macroglobulin could be used as a prognostic marker of the severity of acute pancreatitis. ..
  46. Bonacci G, Cáceres L, Sanchez M, Chiabrando G. Activated alpha(2)-macroglobulin induces cell proliferation and mitogen-activated protein kinase activation by LRP-1 in the J774 macrophage-derived cell line. Arch Biochem Biophys. 2007;460:100-6 pubmed
    ..These results suggest that alpha(2)M*/LRP-1 interaction constitutes a key role in the macrophage functioning during inflammation and cancer. ..
  47. Zhou Y, Zhang Z, Chan P, He X, Tang M, Wu C, et al. Genetic association between low-density lipoprotein receptor-related protein gene polymorphisms and Alzheimer's disease in Chinese Han population. Neurosci Lett. 2008;444:109-11 pubmed publisher
    ..26). Our data suggested that the polymorphism of LRP C766T was strongly associated with AD and T allele might be a protective factor for AD in Chinese Han population. ..
  48. Ramacciotti E, Hawley A, Wrobleski S, Myers D, Strahler J, Andrews P, et al. Proteomics of microparticles after deep venous thrombosis. Thromb Res. 2010;125:e269-74 pubmed publisher
    ..Further studies are needed to confirm the mechanistic role of these proteins in the pathogenesis of venous thrombosis in humans. ..
  49. Zouhir S, Robert Genthon M, Trindade D, Job V, Nedeljkovic M, Breyton C, et al. Assembly of an atypical ?-macroglobulin complex from Pseudomonas aeruginosa. Sci Rep. 2018;8:527 pubmed publisher
  50. Riely G, Rachmilewitz J, Koo P, Tykocinski M. alpha2-macroglobulin modulates the immunoregulatory function of the lipocalin placental protein 14. Biochem J. 2000;351 Pt 2:503-8 pubmed
    ..Moreover, this represents the first documented interaction between the protein carrier alpha(2)M and a lipocalin protein. ..
  51. Adler V, Davidowitz E, Tamburi P, Rojas P, Grossman A. Alpha2-macroglobulin is a potential facilitator of prion protein transformation. Amyloid. 2007;14:1-10 pubmed
    ..Purification of proteins from this fraction led to the identification of alpha2-macroglobulin as an active component suggesting that it may facilitate conformational changes in prion protein in spontaneous forms of prion disease. ..
  52. van Esch S, van Diepen A, Struijk D, Krediet R. The Mutual Relationship Between Peritonitis and Peritoneal Transport. Perit Dial Int. 2016;36:33-42 pubmed publisher
    ..This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. ..
  53. Hu C, Sung S, Liu H, Hsu W, Lee L, Lee C, et al. Genetic risk factors of sporadic Alzheimer's disease among Chinese in Taiwan. J Neurol Sci. 2000;181:127-31 pubmed
    ..The other candidate genes in this study were not associated with the occurrence of AD. In addition, there are no gene-gene interactions. ..
  54. Nacmias B, Tedde A, Cellini E, Forleo P, Orlacchio A, Guarnieri B, et al. Alpha2-macroglobulin polymorphisms in Italian sporadic and familial Alzheimer's disease. Neurosci Lett. 2001;299:9-12 pubmed
    ..Our data do not confirm these associations, in particular we found a significant decrease of the deletion allele in AD with respect to controls. Our data do not support a role for the A2M gene as genetic risk factor for AD. ..
  55. Zhang Y, Ge G, Greenspan D. Inhibition of bone morphogenetic protein 1 by native and altered forms of alpha2-macroglobulin. J Biol Chem. 2006;281:39096-104 pubmed
    ..These findings suggest possible therapeutic interventions involving ectopic expression of modified versions of alpha(2)-macroglobulin in the treatment of fibrotic conditions. ..
  56. Li X, Ye L, Ge Y, Yuan K, Zhang Y, Liang Y, et al. In utero perfluorooctane sulfonate exposure causes low body weights of fetal rats: A mechanism study. Placenta. 2016;39:125-33 pubmed publisher
    ..PFOS exposure may alter placental development and function, causing intrauterine growth restriction via inhibiting placental 11?-hydroxysteroid dehydrogenase 2. ..
  57. Nicosia F, Alberici A, Benussi L, Gasparini L, Ghidoni R, Mazzoli F, et al. Analysis of alpha-2-macroglobulin-2 allele as a risk factor in Alzheimer's disease. Dement Geriatr Cogn Disord. 2001;12:305-8 pubmed
    ..89) or genotype frequency (p = 0.97) in the two different clinical series and in control subjects. The frequencies were not significantly different after stratification by APOE epsilon4 status. ..
  58. Huang M, Austin C, Sari M, Rahmanto Y, Ponka P, Vyoral D, et al. Hepcidin bound to ?2-macroglobulin reduces ferroportin-1 expression and enhances its activity at reducing serum iron levels. J Biol Chem. 2013;288:25450-65 pubmed publisher
    ..A model is proposed that suggests that unlike proteases, which are irreversibly bound to activated ?2M, hepcidin remains labile and available to down-regulate Fpn1. ..
  59. Mettenburg J, Webb D, Gonias S. Distinct binding sites in the structure of alpha 2-macroglobulin mediate the interaction with beta-amyloid peptide and growth factors. J Biol Chem. 2002;277:13338-45 pubmed
    ..These studies suggest a model in which alpha(2)M has three protein interaction sites with distinct specificities, mediating the interaction with Abeta, growth factors, and LRP. ..
  60. Birkenmeier G, Muller R, Huse K, Forberg J, Glaser C, Hedrich H, et al. Human alpha2-macroglobulin: genotype-phenotype relation. Exp Neurol. 2003;184:153-61 pubmed
    ..However, it can be speculated that the observed general age-related alpha2-M deficiency may lead to accelerated accumulation of amyloid-beta, which might be relevant to AD pathology. ..
  61. Tayade C, Esadeg S, Fang Y, Croy B. Functions of alpha 2 macroglobulins in pregnancy. Mol Cell Endocrinol. 2005;245:60-6 pubmed
    ..Here, we review the A2M gene families of mice and humans, the predicted structural relationships between A2M and its pregnancy induced forms and the postulated roles for this gene family in normal pregnancy. ..
  62. Ozawa D, Hasegawa K, Lee Y, Sakurai K, Yanagi K, Ookoshi T, et al. Inhibition of beta2-microglobulin amyloid fibril formation by alpha2-macroglobulin. J Biol Chem. 2011;286:9668-76 pubmed publisher
  63. Shemesh C, Yu R, Gaus H, Seth P, Swayze E, Bennett F, et al. Pharmacokinetic and Pharmacodynamic Investigations of ION-353382, a Model Antisense Oligonucleotide: Using Alpha-2-Macroglobulin and Murinoglobulin Double-Knockout Mice. Nucleic Acid Ther. 2016;26:223-35 pubmed publisher
    ..Binding to A2M could mediate ASOs to nonproductive compartments, and thus, decreased binding of ASOs to A2M could potentially improve ASO pharmacology. ..
  64. McIlroy S, Dynan K, Vahidassr D, Lawson J, Patterson C, Passmore P. Common polymorphisms in LRP and A2M do not affect genetic risk for Alzheimer disease in Northern Ireland. Am J Med Genet. 2001;105:502-6 pubmed
    ..The results from this study indicate that polymorphisms in LRP and A2M are not associated with increased risk for AD in Northern Ireland. ..
  65. Zappia M, Cittadella R, Manna I, Nicoletti G, Andreoli V, Bonavita S, et al. Genetic association of alpha2-macroglobulin polymorphisms with AD in southern Italy. Neurology. 2002;59:756-8 pubmed
    ..Moreover, subjects carrying the A2M genotype I/I-Val/Val had a threefold increase of risk for AD. These data support a population-based susceptibility for AD linked to A2M polymorphisms. ..
  66. Chhina S, Rathore A, Juneja S. Alpha-2-Macroglobulin Levels in Gingival Crevicular Fluid Pre- and Post-scaling and Root Planing with Adjunctive Tetracycline Fibers in Chronic Periodontitis: A Randomized Controlled Trial. J Contemp Dent Pract. 2015;16:474-8 pubmed
    ..001). Clinical and biochemical variables showed a more favorable outcome when SRP was combined with LDD of tetracycline fibers in management of patients suffering from chronic periodontitis. ..
  67. Lu Y, Chen X, Yin Z, Zhu S, Wu D, Chen X. Screening for potential serum biomarkers in rat mesangial proliferative nephritis. Proteomics. 2016;16:1015-22 pubmed publisher
    ..Overall, this study explored a group of candidate biomarkers of mesangial proliferation inducing kidney injury, to provide the basis of an assessment model for MesPGN in the future. ..
  68. Shibata M, Sakai H, Sakai E, Okamoto K, Nishishita K, Yasuda Y, et al. Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E. Eur J Biochem. 2003;270:1189-98 pubmed
    ..These results suggest the possible involvement of cathepsin E in disruption of the structural and functional integrity of alpha 2M in the endolysosome system. ..
  69. Cai L, Tang G, Chen L, Zhang B, Jiang S, Ren D. Genetic studies of A2M and BACE1 genes in Chinese Han Alzheimer's disease patients. Neuroreport. 2005;16:1023-6 pubmed
    ..Through combination-analysis of the data about the A2M-I/D and the A2M-Ile1000Val variants, the A2M gene was suggested to be associated with Alzheimer's disease. ..
  70. Yuan Q, Wang F, Xue S, Jia J. Association of polymorphisms in the LRP1 and A2M genes with Alzheimer's disease in the northern Chinese Han population. J Clin Neurosci. 2013;20:253-6 pubmed publisher
    ..001), but no interaction between LRP1 and A2M genotypes. Our results suggest that the T allele of the LRP1 C766T polymorphism is associated with a decreased risk of SAD in APOE ?4 carriers from the Northern Han Chinese population. ..
  71. Carli A, Harvey E, Azeddine B, Gao C, Li Y, Li A, et al. Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis incidence in a rat model. J Orthop Res. 2017;35:1183-1194 pubmed publisher
    ..2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1183-1194, 2017. ..
  72. Blacker D, Wilcox M, Laird N, Rodes L, Horvath S, Go R, et al. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet. 1998;19:357-60 pubmed
  73. Gonzalez P, Alvarez R, Reguero J, Batalla A, Alvarez V, Cortina A, et al. Variation in the lipoprotein receptor-related protein, alpha2-macroglobulin and lipoprotein receptor-associated protein genes in relation to plasma lipid levels and risk of early myocardial infarction. Coron Artery Dis. 2002;13:251-4 pubmed
    ..0065; odds ratio = 2.18, 95% confidence intervals = 1.22-3.90). According to our data, the variation at the LRPAP1 gene could contribute to the risk of developing an early episode of MI. ..
  74. Styczynska M, Religa D, Pfeffer A, Luczywek E, Wasiak B, Styczynski G, et al. Simultaneous analysis of five genetic risk factors in Polish patients with Alzheimer's disease. Neurosci Lett. 2003;344:99-102 pubmed
    ..Our results suggest that the APOE epsilon 4 allele is the only known genetic risk factor for late-onset, sporadic AD. ..
  75. Nascimento A, Cajazeiras J, Nascimento K, Nogueira S, Sousa B, Teixeira E, et al. Expression, purification and structural analysis of recombinant rBdh-2His?, a spermadhesin from buck (Capra hircus) seminal plasma. Reprod Fertil Dev. 2012;24:580-7 pubmed publisher
    ..The structure of rBdh-2His? remained stable up to 35°C. However, significant structural changes were observed at temperatures higher than 40 °C related to a distortion of the CD spectrum. ..
  76. Thieme R, Kurz S, Kolb M, Debebe T, Holtze S, Morhart M, et al. Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma. PLoS ONE. 2015;10:e0130470 pubmed publisher
    ..This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the anti-aging mechanisms in the NMR. ..
  77. Zhang Y, Wei X, Browning S, Scuderi G, Hanna L, Wei L. Targeted designed variants of alpha-2-macroglobulin (A2M) attenuate cartilage degeneration in a rat model of osteoarthritis induced by anterior cruciate ligament transection. Arthritis Res Ther. 2017;19:175 pubmed publisher
    ..The targeted variants of A2M have a chondroprotective effect similar to wt-A2M. However, A2M-108 variant has enhanced function to attenuate cartilage degeneration compared with wt-A2M. ..
  78. Cattaneo A, Cattane N, Malpighi C, Czamara D, Suarez A, Mariani N, et al. FoxO1, A2M, and TGF-β1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses. Mol Psychiatry. 2018;: pubmed publisher
    ..We therefore provide a successful 'hypothesis-free' approach for the identification and prioritization of candidate genes for GxE interaction studies that can be investigated in GWAS datasets. ..
  79. Falkenberg C, Grubb A, Akerstrom B. Isolation of rat serum alpha 1-microglobulin. Identification of a complex with alpha 1-inhibitor-3, a rat alpha 2-macroglobulin homologue. J Biol Chem. 1990;265:16150-7 pubmed
    ..alpha 1-m complex and free alpha 1-m were determined as 0.16 and 0.010 g/liter, respectively. Thus, alpha 1I3.alpha 1-m constitutes 1-3% of the total alpha 1I3 in rat serum (w/w) and approximately 60% of the total alpha 1-m. ..
  80. Møllgård K, Dziegielewska K, Saunders N, Zakut H, Soreq H. Synthesis and localization of plasma proteins in the developing human brain. Integrity of the fetal blood-brain barrier to endogenous proteins of hepatic origin. Dev Biol. 1988;128:207-21 pubmed
  81. Sun Y, Shi J, Zhang S, Tang M, Liu X, Wang Y, et al. [No evidence for genetic association between alpha-2 macroglobulin I1000V polymorphism and sporadic Alzheimer's disease in two independent Chinese populations]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005;22:174-9 pubmed
    ..The results of this study revealed no association between the I1000V polymorphism of A2M and Chinese sporadic AD in Guangzhou and Chengdu. ..
  82. Meier U, Billich A, Mann K, Schramm H, Schramm W. alpha 2-Macroglobulin is cleaved by HIV-1 protease in the bait region but not in the C-terminal inter-domain region. Biol Chem Hoppe Seyler. 1991;372:1051-6 pubmed
    ..In AIDS, therefore, HIV protease from infected cells in unlikely to interfere with receptor-binding of alpha 2-macroglobulin. ..
  83. Wang X, Luedecking E, Minster R, Ganguli M, Dekosky S, Kamboh M. Lack of association between alpha2-macroglobulin polymorphisms and Alzheimer's disease. Hum Genet. 2001;108:105-8 pubmed
    ..In conclusion, we observed no association between either the intronic deletion polymorphism or the Ile1000Val polymorphism of A2M and AD in our case-control cohort. ..
  84. Toombs C. Alfimeprase: pharmacology of a novel fibrinolytic metalloproteinase for thrombolysis. Haemostasis. 2001;31:141-7 pubmed
    ..As a result, systemic bleeding complications have been greatly reduced due to the inhibitory effects of alpha(2)-macroglobulin. This article reviews the biochemical in vitro and in vivo characteristics of this novel acting thrombolytic. ..
  85. Zhang P, Yang Z, Wan C, Zheng W, Zhang C, Li S, et al. Neither the tumor necrosis factor alpha-308 A/G polymorphism nor the alpha2-macroglobulin polymorphism was associated with late-onset Alzheimer's disease in the Chinese population. Yi Chuan Xue Bao. 2004;31:1-6 pubmed
    ..01) neither the frequencies of genotypes nor alleles of the TNF alpha-308 A/G and A2M polymorphisms were significantly different between AD and controls,suggesting the two polymorphisms were not risk factors to LOAD in Chinese. ..
  86. Lin V, Wang S, Boetticher N, Vazquez D, Saboorian H, McConnell J, et al. Alpha(2) macroglobulin, a PSA binding protein, is expressed in human prostate stroma. Prostate. 2005;63:299-308 pubmed
    ..Considering the unique features of its protein binding and targeting properties, alpha(2)-M expressed in the prostate may play an important role in regulating benign and malignant prostatic growth. ..
  87. Xiao Y, Zhang B. [Association of the polymorphism in alpha-2 macroglobulin gene with essential tremor and Parkinson's disease]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006;23:84-5 pubmed
    ..2) There might be no association of polymorphism at the site of I/D with PD and ET in North China. ..
  88. Shiu Y, Chiu K, Huynh T, Liu P, Liu C. Plasma immune protein analysis in the orange-spotted grouper Epinephelus coioides: Evidence for altered expressions of immune factors associated with a choline-supplemented diet. Fish Shellfish Immunol. 2017;65:235-243 pubmed publisher
  89. Sauer H, Ravindran F, Beldoch M, Sharifpanah F, Jedelská J, Strehlow B, et al. ?2-Macroglobulin enhances vasculogenesis/angiogenesis of mouse embryonic stem cells by stimulation of nitric oxide generation and induction of fibroblast growth factor-2 expression. Stem Cells Dev. 2013;22:1443-54 pubmed publisher
    ..In conclusion, ?2M stimulates endothelial and early cardiac, but not smooth muscle differentiation of ES cells through generation of NO, activation of ERK1/2 as well as PI3K, and induction of FGF-2 expression. ..
  90. Westwood S, Leoni E, Hye A, Lynham S, Khondoker M, Ashton N, et al. Blood-Based Biomarker Candidates of Cerebral Amyloid Using PiB PET in Non-Demented Elderly. J Alzheimers Dis. 2016;52:561-72 pubmed publisher
    ..As in previous studies, acute phase reactants and inflammatory markers dominate this signature. ..