Редактирование: A2M

Alpha-2-macroglobulin precursor (Alpha-2-M) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5) [CPAMD5] [FWP007]

==Publications==

{{medline-entry
|title=Age-Dependent Variation in Glycosylation Features of Alpha-2-Macroglobulin.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31489526
|abstract=Alpha-2-macroglobulin ([[A2M]]) is a glycosylated broad spectrum inhibitor of numerous proteases, including those involved in blood coagulation. Glycosylation characteristics can affect protein structure and function. This study compares glycosylation characteristics of [[A2M]] in newborn umbilical cord (NUCP) and adult pooled plasmas. Peptide N-Glycosidase F treatment was used to evaluate the total N-glycan content of the molecules. Neuraminidase treatment, and affinity for Ricinus Communis Agglutinin I were used to examine terminal sialic acid and galactose content, respectively. Two-dimensional (2D) electrophoresis was used to determine charge-related isoform profiles and fluorophore-assisted carbohydrate electrophoresis (FACE) was used to characterize N-glycan profiles. Results revealed no difference in total N-glycan mass, however, a statistically significant difference was shown in the change in charge associated with sialic acid loss in the NUCP [[A2M]] population. 2D electrophoresis indicated a lower pI range for NUCP [[A2M]] isoforms. In addition, NUCP [[A2M]] displayed a trend toward higher terminal galactose quantities than adult [[A2M]]. FACE revealed an increased abundance of more branched, higher molecular weight glycans in NUCP [[A2M]]. These differences in glycan branching and charged residues may impact [[A2M]] receptor-based clearance and thus could be responsible for the increased [[A2M]] concentration seen in NUCP, and newborns.
|mesh-terms=* Adult
* Aging
* Electrophoresis, Gel, Two-Dimensional
* Glycosylation
* Humans
* Infant, Newborn
* Polysaccharides
* Pregnancy-Associated alpha 2-Macroglobulins
* Protein Isoforms
* Umbilical Cord
|keywords=* Alpha-2-macroglobulin
* Glycosylation
* Newborn
* Plasma
|full-text-url=https://sci-hub.do/10.1007/s12013-019-00883-4
}}
{{medline-entry
|title=[[MMP2]]-[[A2M]] interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29464020
|abstract=Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, [[A2M]] and [[MMP2]], which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein-protein interaction (PPI). Both mRNA and protein levels of [[MMP2]] and [[A2M]] were increased during aging. Furthermore, the interaction between [[MMP2]] and [[A2M]] was verified by immunoprecipitation and immunohistochemistry. [[MMP2]] activity was further measured under the presence or absence of [[A2M]]-[[MMP2]] interaction. [[MMP2]] activity, which was increased under the absence of [[A2M]]-[[MMP2]] interaction, was significantly decreased under the presence of interactions in aged kidney. We further hypothesized that the interaction between [[A2M]]-[[MMP2]] played a role in the inactivation of [[MMP2]] leading to accumulation of ECM including collagen type I and IV. Aged kidney showed highly accumulated [[MMP2]] substrate proteins despite of increased [[MMP2]] protein expression and CR blunted these accumulation. Additional [i]in vivo[/i] analysis revealed that the signal transducer and activator of transcription (STAT) 3 transcriptional factor was significantly increased thus increasing [[A2M]] expression during aging. [[STAT3]] activating cytokines were also highly increased in aged kidney. In conclusion, the results of the present study indicate that [[A2M]]-[[MMP2]] interaction has a role in age-associated renal ECM accumulation and in the suppression such fibrosis by CR.

|keywords=* A2M
* Aging
* Gerotarget
* MMP2
* extracellular matrix
* renal fibrosis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814160
}}
{{medline-entry
|title=[[SPARCL1]] Accelerates Symptom Onset in Alzheimer's Disease and Influences Brain Structure and Function During Aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29154276
|abstract=We recently reported that alpha-2 macroglobulin ([[A2M]]) is a biomarker of neuronal injury in Alzheimer's disease (AD) and identified a network of nine genes co-expressed with [[A2M]] in the brain. This network includes the gene encoding [[SPARCL1]], a protein implicated in synaptic maintenance. Here, we examine whether [[SPARCL1]] is associated with longitudinal changes in brain structure and function in older individuals at risk for AD in the Baltimore Longitudinal Study of Aging. Using data from the Gene-Tissue Expression Project, we first identified two single nucleotide polymorphisms (SNPs), rs9998212 and rs7695558, associated with lower brain [[SPARCL1]] gene expression. We then analyzed longitudinal trajectories of cognitive performance in 591 participants who remained cognitively normal (average follow-up interval: 11.8 years) and 129 subjects who eventually developed MCI or AD (average follow-up interval: 9.4 years). Cognitively normal minor allele carriers of rs7695558 who developed incident AD showed accelerated memory loss prior to disease onset. Next, we compared longitudinal changes in brain volumes (MRI; n = 120 participants; follow-up = 6.4 years; 826 scans) and resting-state cerebral blood flow (rCBF; 15O-water PET; n = 81 participants; follow-up = 7.7 years; 664 scans) in cognitively normal participants. Cognitively normal minor allele carriers of rs9998212 showed accelerated atrophy in several global, lobar, and regional brain volumes. Minor allele carriers of both SNPs showed longitudinal changes in rCBF in several brain regions, including those vulnerable to AD pathology. Our findings suggest that [[SPARCL1]] accelerates AD pathogenesis and thus link neuroinflammation with widespread changes in brain structure and function during aging.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Alzheimer Disease
* Brain
* Calcium-Binding Proteins
* Cerebrovascular Circulation
* Cognition Disorders
* Extracellular Matrix Proteins
* Female
* Humans
* Independent Living
* Longitudinal Studies
* Magnetic Resonance Imaging
* Male
* Middle Aged
* Neuropsychological Tests
* Polymorphism, Single Nucleotide
* Positron-Emission Tomography
|keywords=* Alzheimer’s disease
* magnetic resonance imaging
* positron emission tomography
* single nucleotidepolymorphism
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934753
}}
{{medline-entry
|title=Depletion of potential [[A2M]] risk haplotype for Alzheimer's disease in long-lived individuals.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19639019
|abstract=Risk alleles for age-related diseases are expected to decrease in frequency in the population strata of increasing age. Consistent with this hypothesis, earlier studies showed a depletion of the Alzheimer's disease risk factor APOE*epsilon4 in long-lived individuals (LLIs). To evaluate whether this observation also holds for a previously suggested Alzheimer's disease risk haplotype in the [[A2M]] gene, we analyzed this particular haplotype in 1042 German LLIs (aged 95-100 years) and 1040 younger individuals (aged 60-75 years). Our results show a significant depletion of this haplotype in LLIs, thus confirming it as a mortality factor in the elderly. Consequently, our data support an involvement of the suggested [[A2M]] risk haplotype in the pathogenesis of Alzheimer's disease and adds new evidence to the risk-allele depletion hypothesis.
|mesh-terms=* Aged
* Aged, 80 and over
* Alzheimer Disease
* Apolipoproteins E
* Genetic Predisposition to Disease
* Haplotypes
* Humans
* Longevity
* alpha-Macroglobulins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987169
}}
{{medline-entry
|title=Zinc dyshomeostasis, ageing and neurodegeneration: implications of [[A2M]] and inflammatory gene polymorphisms.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17851198
|abstract=Zinc maintains brain functions because involved in glutaminergic transmission, in antioxidant response and in conferring biological activity to brain enzymes and growth factors. Zinc turnover is mediated by Metallothioneins (MT) which regulate the intracellular free zinc ions [Zn](i). Alterations in zinc homeostasis are associated to various brain dysfunctions, including brain inflammatory status, but little is known about its implication in the aging brain and neurodegeneration. Literature data in experimental animals suggest that zinc dyshomeostasis may occur in aging associated to a decline in brain functions. One of the causes may be an altered homeostasis of MT and other zinc-binding proteins, such as alpha2 macroglobulin ([[A2M]]), which are of protection against stress and inflammation during young/adult age but turn into being harmful in aging. In fact, despite total brain zinc content is unchanged in the brain of aged animals, with respect to the young/adult, the activity of some zinc dependent enzymes is impaired and large amount of zinc has been found in the core of Alzheimer's disease senile plaques. 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.
|mesh-terms=* Aged
* Aging
* Alzheimer Disease
* Brain
* Homeostasis
* Humans
* Nerve Degeneration
* Polymorphism, Genetic
* Zinc
* alpha-Macroglobulins

|full-text-url=https://sci-hub.do/10.3233/jad-2007-12110
}}
{{medline-entry
|title=The genetic association between alpha-2-macroglobulin ([[A2M]]) gene deletion polymorphism and low serum [[A2M]] concentration in overweight/obese Thais.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16910174
|abstract=The study subjects were 192 overweight and obese Thais (BMI > 25.00 kg/m2), and 103 Thai controls (BMI = 18.50-24.99 kg/m2), whose ages ranged from 18-60 years. All subjects were evaluated for serum Alpha-2-macroglobulin ([[A2M]]), globulin, albumin concentration, and polymorphic variation in the [[A2M]] gene. Serum [[A2M]] and albumin were significantly lower in the overweight/obese group (P < 0.05). For the overweight/obese and control group, the median ages were 38 and 37 years, serum [[A2M]] 200.2; 252.0 (mg/L), albumin 4.4; 4.5 (g/dL), and globulin 3.0; 2.95 (g/dL), respectively. [[A2M]] deletion polymorphism genotyping showed no association between [[A2M]] deletion polymorphism and the two groupings. At serum [[A2M]] concentration < 250 mg/L, there was no relationship between [[A2M]] deletion polymorphism and age. Serum [[A2M]] had a significant negative correlation with age in all subjects (R = 0.09, P < 0.05). The results did not support the hypothesis that [[A2M]] deletion polymorphism is associated with a low [[A2M]] concentration in overweight/obese subjects. However, serum [[A2M]] had a significant negative correlation with age; serum [[A2M]] can possibly be used to indicate the aging of cells in vivo, including the brain. Further studies are needed to investigate other [[A2M]] genes located on chromosome 12 to prove [[A2M]] gene polymorphism's association with low serum [[A2M]] and aging.
|mesh-terms=* Adolescent
* Adult
* Aging
* DNA
* Electrophoresis, Polyacrylamide Gel
* Female
* Gene Deletion
* Genotype
* Humans
* Logistic Models
* Male
* Middle Aged
* Obesity
* Odds Ratio
* Polymorphism, Genetic
* Serum Albumin
* Thailand
* alpha-Macroglobulins

|full-text-url=https://sci-hub.do/10.1080/10284150600771777
}}
{{medline-entry
|title=alpha2-macroglobulin in late-onset Alzheimer's disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10959035
|abstract=alpha2-macroglobulin (alpha(2)M) is an abundant plasma protein similar in structure and function to a group of proteins called alpha-macroglobulins. alpha(2)M is also produced in the brain where it binds multiple extracellular ligands and is internalized by neurons and astrocytes. In the brain of Alzheimer's disease (AD) patients, alpha(2)M has been localized to diffuse amyloid plaques. alpha(2)M also binds soluble beta-amyloid, of which it mediates degradation. However, an excess of alpha(2)M can also have neurotoxic effects. Based on genetic evidence, is now recognized as one of the two confirmed late onset AD genes. As for the three early onset genes (the amyloid beta-protein precursor and the two presenilins) and for the other late onset gene (ApoE), DNA polymorphisms in the [[A2M]] gene associated with AD result in significantly increased accumulation of amyloid plaques in AD brains. These data support an important role for [[A2M]] in AD etiopathology.
|mesh-terms=* Age of Onset
* Aging
* Alzheimer Disease
* Humans
* Polymorphism, Genetic
* Structure-Activity Relationship
* alpha-Macroglobulins

|full-text-url=https://sci-hub.do/10.1016/s0531-5565(00)00113-3
}}