Affinage

A2M

Alpha-2-macroglobulin · UniProt P01023

Length
1474 aa
Mass
163.3 kDa
Annotated
2026-06-09
69 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

A2M is a secreted pan-protease inhibitor that operates through a conformational trap: native A2M assembles as a hollow tetramer of two crescent-shaped disulfide-bridged subunit dimers held together largely by linker (LNK)-region contacts, and bait-region cleavage triggers intrasubunit domain repositioning that collapses the tetramer into a compact, protease-enclosing conformation (PMID:33964423). This conformational change depends not on proteolysis alone but on lysis of the internal thiol ester, and the collapsed form retains LRP1-binding for receptor-mediated clearance (PMID:33301305). Beyond trapping proteases, A2M directly binds and neutralizes cytokines and growth factors: it captures IL-1β to block downstream NF-κB-driven catabolism in chondrocytes (PMID:35451533), binds TGF-β1 and amyloid-β through its bait region and N-terminal domain (PMID:14678766, PMID:21320498), and an N-glycosylation-site mutation (p.N410T) that weakens A2M–Aβ interaction has been identified in Alzheimer's disease (PMID:36698894). A2M also sequesters and inhibits matrix metalloproteinases (MMP2), driving extracellular matrix accumulation (PMID:29464020). Its expression is transcriptionally activated through defined promoter elements by NR4A receptors via an NGFI-B response element in vascular smooth muscle cells (PMID:25809189) and by STAT3 (PMID:29464020), and through these inputs A2M modulates PI3K/AKT, SMAD, and RhoA-GTPase signaling in contexts spanning tumor adhesion and migration (PMID:29281661), uterine spiral-artery smooth-muscle phenotype switching in preeclampsia (PMID:39994728), and skeletal stem/progenitor cell fate (PMID:37965574).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 Medium

    Established that an AD-associated A2M intronic deletion alters cytokine binding rather than the canonical protease-trap function, separating A2M's two activities.

    Evidence SDS-PAGE, conformational and binding assays on plasma from deletion-homozygous AD patients

    PMID:14678766

    Open questions at the time
    • Mechanism connecting the intronic deletion to altered TGF-β1/Aβ binding not defined
    • Small sample size
    • No structural basis for differential binding
  2. 2011 Medium

    Mapped the protein regions required for A2M's dual proteinase- and cytokine-trapping, showing bait region and N-terminal domain modification inactivates both functions.

    Evidence In vitro MAA adduct formation and binding/NO assays using recombinant mouse A2M fragments

    PMID:21320498

    Open questions at the time
    • Uses mouse fragments, not intact human tetramer
    • Physiological relevance of MAA adduction unclear
    • Single lab
  3. 2015 High

    Identified a direct transcriptional input controlling A2M, showing NR4A receptors bind the A2M promoter and link its expression to MMP regulation in vascular cells.

    Evidence Luciferase, EMSA, ChIP, overexpression/knockdown, zymography, transgenic mouse in VSMCs

    PMID:25809189

    Open questions at the time
    • Other promoter regulators not surveyed
    • Extent of MMP suppression mediated by A2M only partial
  4. 2017 Medium

    Linked A2M to intracellular signaling control, showing it suppresses tumor cell PI3K/AKT and SMAD pathways via miR-21/PTEN without inducing EMT.

    Evidence In vitro adhesion/migration assays, Western blot, miR-21 measurement, xenografts

    PMID:29281661

    Open questions at the time
    • Receptor/mechanism coupling extracellular A2M to miR-21 not defined
    • No direct binding partner identified
  5. 2017 Medium

    Demonstrated A2M directly traps and inhibits MMP2 and is driven by STAT3, establishing an aging-associated A2M–MMP2–ECM accumulation axis.

    Evidence Co-IP, MMP2 activity assay, RNA-seq, IHC in aged rat kidney

    PMID:29464020

    Open questions at the time
    • Co-IP not reciprocally validated in human tissue
    • Whether trapping uses the canonical conformational mechanism unconfirmed
  6. 2020 High

    Resolved the mechanistic basis of the conformational trap, showing thiol ester lysis (not proteolysis alone) drives the collapse while LRP1-binding is retained.

    Evidence Recombinant Q975C thiol ester mutant with protease inhibition and LRP1 binding assays

    PMID:33301305

    Open questions at the time
    • Quantitative coupling between thiol ester lysis and bait cleavage kinetics not fully defined
  7. 2021 High

    Defined the architecture of the native trap, revealing the hollow LNK-linked tetramer and the collapse geometry that encloses captured protease.

    Evidence Negative-stain EM, SAXS, XL-MS, and engineered intersubunit disulfide mutagenesis

    PMID:33964423

    Open questions at the time
    • No high-resolution atomic structure of trapped protease complex
    • Conformational intermediates not captured
  8. 2022 Medium

    Showed A2M directly binds IL-1β to block NF-κB catabolic signaling, extending the cytokine-neutralizing role to cartilage homeostasis.

    Evidence Reciprocal IP, fluorescence microscopy, Western blot, qRT-PCR in human C28 chondrocytes

    PMID:35451533

    Open questions at the time
    • Whether IL-1β capture uses bait region or trap mechanism not resolved
    • Cytoplasmic localization of A2M not mechanistically explained
  9. 2023 Medium

    Provided patient-level evidence linking A2M to Aβ clearance, showing an N-glycosylation-eliminating mutation weakens A2M–Aβ binding.

    Evidence Whole-exome sequencing, structure prediction, Co-IP from patient plasma

    PMID:36698894

    Open questions at the time
    • Single case
    • Causal contribution to disease not established by rescue
    • Co-IP not reciprocally validated
  10. 2023 Medium

    Implicated A2M as a regulator of stem/progenitor fate, with loss biasing mesenchymal cells toward adipogenesis over osteogenesis.

    Evidence siRNA loss-of-function in human BM-MSCs, differentiation assays, in vivo RNA-seq

    PMID:37965574

    Open questions at the time
    • Molecular pathway coupling A2M to lineage choice undefined
    • No rescue with recombinant A2M
  11. 2025 Medium

    Connected A2M to RhoA-GTPase-driven smooth-muscle phenotype switching in preeclampsia, with LRP1 blockade reversing the phenotype.

    Evidence Co-IP, LC-MS/MS, AAV knockdown, RAP-mediated LRP1 blockade in rat preeclampsia model

    PMID:39994728

    Open questions at the time
    • Direct vs indirect interaction with RhoA pathway components unresolved
    • Human validation limited
  12. 2025 Medium

    Showed A2M can reprogram macrophage polarization toward M2 and promote osteogenesis through IL-4 signaling.

    Evidence Exosome-delivered A2M, shRNA IL-4 rescue, rat ONFH model

    PMID:41203607

    Open questions at the time
    • How A2M activates IL-4 signaling mechanistically unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how A2M's extracellular conformational trap and LRP1 clearance mechanistically couple to the diverse intracellular signaling outcomes (NF-κB, PI3K/AKT, SMAD, RhoA, IL-4) attributed to it across tissues.
  • No unifying receptor/signaling model linking A2M binding to downstream pathway modulation
  • Most signaling roles shown in single labs without reciprocal mechanistic validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140313 molecular sequestering activity 3
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
ALKIL1BLRP1MMP2TGFB1

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Native human A2M forms a hollow tetrameric conformation composed of two crescent-shaped disulfide-bridged subunit dimers with a central hollow space and minimal inter-dimer interactions mediated mainly by linker (LNK) regions. Bait region cleavage induces intrasubunit domain repositioning and collapse of the tetramer into a compact conformation that encloses an interior protease-trapping cavity. A recombinant A2M with an engineered intersubunit disulfide in the LNK region confirmed predicted LNK–LNK interactions in native A2M. Negative stain electron microscopy, small-angle X-ray scattering (SAXS), cross-linking mass spectrometry (XL-MS), and recombinant A2M mutagenesis Molecular & Cellular Proteomics High 33964423
2020 Replacing the thiol ester motif (CGEQ) of A2M with a disulfide-forming sequence (CGEC) in mutant A2M Q975C produces a correctly folded, native-conformation tetramer that undergoes proteolysis-induced conformational collapse and retains LRP1-binding. However, the mutant had decreased trypsin-inhibitory capacity and was more susceptible to protease cleavage, demonstrating that thiol ester lysis (not proteolysis alone) contributes to the conformational change mechanism. Recombinant protein expression, mass spectrometry, electrophoretic mobility assay, protease inhibition assay, LRP1 binding assay Biochemistry High 33301305
2022 A2M binds and neutralizes IL-1β, blocking downstream NF-κB-induced catabolism in human chondrocytes. Immunoprecipitation confirmed direct A2M–IL-1β binding; fluorescence microscopy localized A2M to the cytoplasm after incubation. A2M reduced NF-κB, MMPs, and TNF-α levels and increased cartilage-protective gene expression (Col2, Smad4, aggrecan) in a dose-dependent manner. Immunoprecipitation, fluorescence microscopy (VivoTag-labeled A2M), Western blot, qRT-PCR in human chondrocyte cell line C28 Journal of Orthopaedic Research Medium 35451533
2017 A2M modulates tumor cell adhesion, migration, and growth by inhibiting PI3K/AKT and SMAD signaling pathways, upregulating PTEN via downregulation of miR-21, and increasing CD29 and CD44 expression, without inducing EMT, as shown in vitro and in tumor xenografts. Cell-based assays (adhesion, migration, growth), Western blot for pathway components, miR-21 measurement, xenograft mouse model, transcriptome analysis of A2M-treated cells PLoS One Medium 29281661
2015 NR4A receptors (NOR-1, Nurr1, Nur77) directly transcriptionally activate the human A2M promoter via an NGFI-B response element (NBRE at -71/-64), increasing A2M expression and secretion in vascular smooth muscle cells (VSMCs). A2M upregulation by NR4A receptors partially mediates their inhibitory effect on MMP-2 and MMP-9 activity. Luciferase reporter assay, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), lentiviral overexpression, NR4A knockdown, zymography, transgenic mouse model Thrombosis and Haemostasis High 25809189
2017 A2M interacts directly with MMP2 in aged rat kidney (confirmed by immunoprecipitation), and this interaction suppresses MMP2 enzymatic activity, leading to accumulation of ECM substrates including collagen type I and IV. STAT3 transcriptional activation (elevated by aging-associated cytokines) drives increased A2M expression, which promotes MMP2 trapping and ECM accumulation. Immunoprecipitation, immunohistochemistry, MMP2 activity assay (with and without A2M), RNA-seq, real-time PCR, Western blot in aged rat kidney Oncotarget Medium 29464020
2023 A novel heterozygous missense mutation in A2M (c.1229A>C, p.N410T) eliminates an N-glycosylation site (Asn410) required for A2M activation and Aβ binding. Co-immunoprecipitation from patient plasma showed weakened interaction between mutant A2M and amyloid-β compared to wild-type, establishing a mechanism by which this mutation impairs Aβ clearance. Whole-exome sequencing, 3D protein structure prediction, co-immunoprecipitation from patient plasma Frontiers in Neurology Medium 36698894
2003 Plasma A2M from AD patients homozygous for the A2M intronic deletion showed normal subunit size, conformation, and protease inhibitory activity, but displayed markedly increased TGF-β1 binding and modestly elevated Aβ binding (in methylamine-activated form) compared to non-deletion patients, suggesting the deletion affects cytokine binding rather than protease trapping. SDS-PAGE, conformational assays, trypsin binding assay, TGF-β1 binding assay, Aβ binding assay on human plasma samples Neurobiology of Disease Medium 14678766
2011 Malondialdehyde-acetaldehyde (MAA) adduct formation on the A2M bait region (residues 620–792) and A2M N-terminal domain (residues 168–230) abrogates bait region binding to TGF-β1, trypsin, and elastase, and suppresses TGF-β1-induced NO production, indicating that chemical modification of these domains inactivates A2M's proteinase- and cytokine-trapping functions. In vitro MAA adduct formation, binding assays (trypsin, elastase, TGF-β1), NO production assay using mouse A2M recombinant fragments FEBS Letters Medium 21320498
2025 A2M directly upregulates RhoA-GTPase activity in smooth muscle cells (SMCs) of the uterine spiral arteries, promoting SMC phenotype switching disorder that underlies preeclampsia pathology. Blocking A2M–LRP1 interaction with receptor-associated protein (RAP) reversed SMC phenotype switching and alleviated preeclampsia in a rat model. LC-MS/MS and Co-IP confirmed A2M interaction with components of the RhoA-GTPase pathway. Co-immunoprecipitation, LC-MS/MS proteomics, proteomic sequencing of A2M-overexpressing rat placenta, RAP-mediated A2M–LRP1 blockade in rat preeclampsia model, AAV knockdown, cytological and explant experiments Cell Communication and Signaling Medium 39994728
2030 A2M silencing (CRISPR/Cas9) in STAD cells decreased cell viability, migration, invasion, and colony formation, and reduced expression of vimentin, indicating that A2M promotes epithelial-mesenchymal transition (EMT) in stomach adenocarcinoma through upregulation of vimentin. CRISPR/Cas9 knockdown, cell viability assay, migration/invasion (Transwell), colony formation, Western blot for vimentin in STAD cell lines Translational Cancer Research Medium 42180958
2023 A2M silencing in human bone marrow mesenchymal stromal cells (BM-MSCs) induced proliferation and skewed lineage differentiation toward adipogenesis at the expense of osteogenesis, recapitulating aspects of age-induced stem cell dysfunction and implying a role for A2M as a regulator of skeletal stem/progenitor cell fate. RNA-seq in mouse SSPCs, siRNA loss-of-function in human BM-MSCs, differentiation assays, FACS, micro-CT Frontiers in Cell and Developmental Biology Medium 37965574
2014 A chromosomal translocation t(2;12)(p23;p13) generates a novel A2M–ALK chimeric fusion gene in which exon 22 of A2M is fused to exon 19 of ALK, identified in a fetal lung interstitial tumor (FLIT). This fusion results in ALK expression in mesenchymal tumor cells, linking A2M as an ALK fusion partner with potential oncogenic signaling. Karyotyping (FISH break-apart), 5'-RACE, RT-PCR, genomic sequencing confirming breakpoint in A2M intron 22 and ALK intron 18 Genes, Chromosomes and Cancer Medium 24965693
2024 In sea cucumber (Apostichopus japonicus), the A2M thioester domain (TED) binds directly to pathogens and causes bacterial aggregation, while the receptor-binding domain (RBD) interacts with GRP78 (AjGRP78), which then accelerates lysosomal degradation of bacteria by facilitating cytoskeletal polymerization and rearrangement, promoting phagocytosis. Recombinant domain cloning, co-immunoprecipitation, phagocytosis assay, lysosomal degradation assay, cytoskeleton imaging in sea cucumber coelomocytes International Journal of Biological Macromolecules Low 38513908
2023 LINC00612 enhances binding of phosphorylated STAT3 (p-STAT3) to the A2M promoter, thereby increasing A2M expression in bronchial epithelial cells (BEAS-2B). RNA antisense purification and ChIP confirmed the interaction between LINC00612, STAT3, and the A2M promoter. A2M knockdown attenuated the anti-apoptotic and anti-inflammatory effects of LINC00612 overexpression. RNA antisense purification, chromatin immunoprecipitation (ChIP), overexpression/knockdown in BEAS-2B cells, flow cytometry apoptosis assay PeerJ Low 36883061
2025 In SH-SY5Y neuroblastoma cells exposed to pesticides (Aldicarb and Chlorpyrifos), exogenous A2M upregulates anti-apoptotic proteins Bcl-2 and Nrf2 while downregulating pro-apoptotic markers Bax, Caspase-3, and Caspase-9. A2M also enhanced mitochondrial complex I and III activity and reduced ROS and inflammatory cytokine-induced DNA damage. Western blot profiling, biochemical mitochondrial enzyme activity assays, ROS measurement in pesticide-exposed SH-SY5Y neuroblastoma cells bioRxiv (preprint)preprint Low bio_10.1101_2025.06.27.661925
2025 Exosome-delivered A2M protein reprogrammed M1 macrophage polarization toward M2 (decreasing TNF-α and IL-6, increasing CD206 and Arg-1) through IL-4 signaling activation, and enhanced osteogenic differentiation of BMSCs (upregulating RUNX2, ALP, OCN). shRNA-mediated IL-4 knockdown abolished these effects, confirming pathway specificity. Engineered exosome delivery of A2M, transcriptomic/proteomic profiling, shRNA IL-4 knockdown, ELISA, Western blot, rat ONFH model with micro-CT Cell Death Discovery Medium 41203607

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1979 Structure of the A2m(1) allotype of human IgA--a recombinant molecule. Proceedings of the National Academy of Sciences of the United States of America 90 286295
2018 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. Molecular psychiatry 72 29302075
2004 Increased risk for Alzheimer disease with the interaction of MPO and A2M polymorphisms. Archives of neurology 42 15023809
1991 A deletion polymorphism in the human alpha-2-macroglobulin (A2M) gene. Nucleic acids research 41 1717945
2022 Mesenchymal Stem Cell-Originated Exosomal Lnc A2M-AS1 Alleviates Hypoxia/Reperfusion-Induced Apoptosis and Oxidative Stress in Cardiomyocytes. Cardiovascular drugs and therapy 40 35543792
2017 The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat. PloS one 39 29281661
2015 NR4A receptors up-regulate the antiproteinase alpha-2 macroglobulin (A2M) and modulate MMP-2 and MMP-9 in vascular smooth muscle cells. Thrombosis and haemostasis 37 25809189
2009 An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 32 19105203
2014 Regulatory mutations in the A2M gene are involved in the mastitis susceptibility in dairy cows. Animal genetics 31 25237709
2007 Zinc dyshomeostasis, ageing and neurodegeneration: implications of A2M and inflammatory gene polymorphisms. Journal of Alzheimer's disease : JAD 30 17851198
2022 A2M inhibits inflammatory mediators of chondrocytes by blocking IL-1β/NF-κB pathway. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 29 35451533
2006 Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease. Journal of the neurological sciences 29 16784755
2001 Common polymorphisms in LRP and A2M do not affect genetic risk for Alzheimer disease in Northern Ireland. American journal of medical genetics 29 11496365
2022 LncRNA A2M-AS1 Promotes Ferroptosis in Pancreatic Cancer via Interacting With PCBP3. Molecular cancer research : MCR 28 35920801
2021 Structural Investigations of Human A2M Identify a Hollow Native Conformation That Underlies Its Distinctive Protease-Trapping Mechanism. Molecular & cellular proteomics : MCP 26 33964423
2010 Association analysis of TNFR2, VDR, A2M, GSTT1, GSTM1, and ACE genes with rheumatoid arthritis in South Asians and Caucasians of East Midlands in the United Kingdom. Rheumatology international 24 20401725
2010 Lack of interaction between LRP1 and A2M polymorphisms for the risk of Alzheimer disease. Neuroscience letters 23 20637261
2005 Association study of the A2M and LRP1 Genes with Alzheimer disease in the Han Chinese. Biological psychiatry 23 16040006
2017 MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction. Oncotarget 22 29464020
1987 IgA2 allotypes determined by restriction fragment length polymorphism in IgA deficiency. Re-expression of the silent A2m(2) allotype in the children of IgA-deficient patients. Journal of immunogenetics 22 2900854
2020 Long Non-Coding RNA A2M-AS1 Promotes Breast Cancer Progression by Sponging microRNA-146b to Upregulate MUC19. International journal of general medicine 21 33273850
2005 Genetic studies of A2M and BACE1 genes in Chinese Han Alzheimer's disease patients. Neuroreport 21 15931081
2016 A proteomics analysis reveals that A2M might be regulated by STAT3 in persistent allergic rhinitis. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20 27228572
2000 Association of APOE promoter but not A2M polymorphisms with risk of developing Alzheimer's disease. Neuroreport 20 11095526
2017 Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene: report of 2 infantile cases and review of the differential diagnosis of infantile pulmonary lesions. Human pathology 18 28705706
1983 Anaphylactic transfusion reaction associated with a possible anti-A2m(1). Clinical and laboratory haematology 18 6583035
2022 Association Between Common Variants of APOE, ABCA7, A2M, BACE1, and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease: Data from the PUMCH Dementia Cohort. Journal of Alzheimer's disease : JAD 16 34958020
2020 LncRNA A2M-AS1 lessens the injury of cardiomyocytes caused by hypoxia and reoxygenation via regulating IL1R2. Genes & genomics 15 33057899
1992 Linkage relations between A2M, HOX3, INT1, KRAS2, and PAH on bovine chromosome 5. Genomics 15 1385300
2014 Identification of novel ALK rearrangement A2M-ALK in a neonate with fetal lung interstitial tumor. Genes, chromosomes & cancer 14 24965693
2020 MFGE8, ALB, APOB, APOE, SAA1, A2M, and C3 as Novel Biomarkers for Stress Cardiomyopathy. Cardiovascular therapeutics 13 32695227
2017 HuoXueJieDu Formula Alleviates Diabetic Retinopathy in Rats by Inhibiting SOCS3-STAT3 and TIMP1-A2M Pathways. International journal of genomics 13 29318137
2021 Reconstruction and Analysis of the Immune-Related LINC00987/A2M Axis in Lung Adenocarcinoma. Frontiers in molecular biosciences 12 33987201
2022 A2M is a potential core gene in intrahepatic cholangiocarcinoma. BMC cancer 11 34979994
2022 Downregulated ADAMTS1 Incorporating A2M Contributes to Tumorigenesis and Alters Tumor Immune Microenvironment in Lung Adenocarcinoma. Biology 11 35625488
2011 Modification of mouse A2M B (620-792) and A2M N (168-230) by malondialdehyde and acetaldehyde attenuates the proteinase and TGF-β1 binding ability of A2MB. FEBS letters 10 21320498
2003 Functional analysis of plasma alpha(2)-macroglobulin from Alzheimer's disease patients with the A2M intronic deletion. Neurobiology of disease 10 14678766
1991 Sequence polymorphism in the human alpha-2-macroglobulin (A2M) gene. Nucleic acids research 10 1707161
2020 Substituting the Thiol Ester of Human A2M or C3 with a Disulfide Produces Native Proteins with Altered Proteolysis-Induced Conformational Changes. Biochemistry 9 33301305
2019 Tissue specific alpha-2-Macroglobulin (A2M) splice isoform diversity in Hilsa shad, Tenualosa ilisha (Hamilton, 1822). PloS one 9 31335900
2020 Association Between FoxO1, A2M, and TGF-β1, Environmental Factors, and Major Depressive Disorder. Frontiers in psychiatry 8 32792993
2010 Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals. European journal of human genetics : EJHG 8 19639019
1993 Localization of ESD and A2M genes to sheep chromosome 3 by in situ hybridization. Cytogenetics and cell genetics 8 7679066
2023 Novel heterozygous mutation in alpha-2-macroglobulin (A2M) suppressing the binding of amyloid-β (Aβ). Frontiers in neurology 7 36698894
2013 Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects. Neurobiology of aging 7 24011543
2012 Association of polymorphisms in the LRP1 and A2M genes with Alzheimer's disease in the northern Chinese Han population. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 7 23186781
2022 Overexpression of lncRNA A2M-AS1 inhibits cell growth and aggressiveness via regulating the miR-587/bone morphogenetic protein 3 axis in lung adenocarcinoma. Human & experimental toxicology 6 36461613
2015 Pharmacogenetic Study on the Impact of Rivastigmine Concerning Genetic Variants of A2M and IL-6 Genes on Iranian Alzheimer's Patients. Molecular neurobiology 6 26289409
2024 A2M possesses anti-bacterial functions by recruiting and enhancing phagocytosis through GRP78 in an echinoderm. International journal of biological macromolecules 5 38513908
2023 LincRNA00612 inhibits apoptosis and inflammation in LPS-induced BEAS-2B cells via enhancing interaction between p-STAT3 and A2M promoter. PeerJ 5 36883061
2016 Polymorphism in the A2M gene associated with high-quality milk in Murrah buffaloes (Bubalus bubalis). Genetics and molecular research : GMR 5 27173184
1976 Germinal derivatives of the En controlling-element system in maize: Characterization of colored, pale and colorless derivatives a2-m. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 5 24413838
2025 Targeting A2M-LRP1 reverses uterine spiral artery remodeling disorder and alleviates the progression of preeclampsia. Cell communication and signaling : CCS 3 39994728
2025 Olfactory mucosal mesenchymal stem cell-derived exosome Lnc A2M-AS1 ameliorates oxidative stress by regulating TP53INP1-mediated mitochondrial autophagy through interacting with IGF2BP1 in Parkinson's diseases. Cell biology and toxicology 3 40111649
1989 The detection of an antibody against IgA allotype A2M 2 and a study of the Am genetic marker among the Han Chinese population. Transfusion 3 2497568
2025 Restoration of A2M reduces drug resistance and malignancy in paclitaxel-resistant lung cancer cells. The international journal of biochemistry & cell biology 2 40345481
2025 Knockdown of p53 Enhances LncRNA A2M-AS1 Inhibition of Pancreatic Cancer Progression via Regulating MAPK Pathway. Cancer medicine 2 40653606
2025 Metabolic glycoengineered exosome-A2M nanoplatform reprograms macrophage polarization and orchestrates bone regeneration in ONFH. Cell death discovery 2 41203607
2023 Spontaneous Partial Regression of Fetal Lung Interstitial Tumor With A2M::ALK Rearrangement in a Neonate. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2 37818649
2010 Association between haplotype -88G/25G in A2M with Alzheimer's disease. Neuroscience letters 2 20493925
2006 The genetic association between alpha-2-macroglobulin (A2M) gene deletion polymorphism and low serum A2M concentration in overweight/obese Thais. Nutritional neuroscience 2 16910174
2024 Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea. Journal of proteome research 1 38407963
2024 Molecular recognition and interaction between human plasminogen Kringle 5 and A2M domain in human complement C5 by biospecific methods coupled with molecular dynamics simulation. International journal of biological macromolecules 1 38754659
2023 Novel role for alpha-2-macroglobulin (A2M) as a disease modifying protein in senile osteoporosis. Frontiers in cell and developmental biology 1 37965574
2026 CGRP/TSP1 Signaling Dampens Corneal Inflammation and Fibrosis by Targeting A2M During Corneal Stromal Wound Healing. Investigative ophthalmology & visual science 0 41533912
2026 A2M promotes the progression of STAD by upregulating vimentin expression and epithelial-mesenchymal transition: boinformatics analysis and experimental verification. Translational cancer research 0 42180958
2025 A2M-AS1, DBH-AS1, and NCBP2-AS2 in breast cancer: expression patterns, CA125-3 association, and a DBH-AS1-NCBP2-AS2 axis. Molecular biology reports 0 41065851
2023 A2M Serves as Promising Biomarker for Chronic Obstructive Pulmonary Disease. International journal of chronic obstructive pulmonary disease 0 37123074
2023 Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) expression analysis and Influence of Separation from Parents in Childhood on the Suicide and Self-injury Behavior and Psychological Adjustment in Adolescence. Cellular and molecular biology (Noisy-le-Grand, France) 0 37213155

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