Involvement of Neuronal Anion Exchange Proteins in Cell Death in Alzheimer's Disease

Bosman, G.J.C.G.M.; Renkawek, K; Workum, F. P. A. van; Bartholomeus, I.G.P.; Grip, W.J. de

doi:10.1159/000213836

Cited by 13 publications

(10 citation statements)

References 49 publications

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“…The functional consequences of changes in anion exchange structure may range from acidosis, disturbance of cytoskeleton integrity, and untimely or impaired recognition of cells by components of the immune system, such as microglia. Microglial cells express a distinct set of pH regulatory carriers that control for a defined level of intracellular pH (80).…”

Section: G Bicarbonate Transportersmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,100

2,981

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Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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Section: G Bicarbonate Transportersmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,100

2,981

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“…29 Changes in band 3 observed with aging include a decrease in efficiency of anion transport (decreased V max ), in spite of an increase in the number of anion binding sites (increased K m ), decrease in glucose transport, binding of antibodies to aged band 3, increase in band 3 degradation to smaller fragments as detected by quantitative binding of antibodies to band 3 breakdown products and amino acid residues 812-830, and in situ binding of physiological IgG autoantibodies resulting in cellular removal (TABLE 3). [7][8][9][10][11][12][13][14][15][16][17][18][19]29,[51][52][53][54][55][56] NOTE: SCAs appeared on stored nucleated cells and platelets because they reduced or abolished the phagocytosis-inducing ability of IgG directed against them. SCIgG from senescent red cells was absorbed with each of the cell types or platelets listed and then tested with target red cells.…”

Section: Sca Is Derived From Bandmentioning

confidence: 99%

“…9). 14,64,78,102,103 One of these, an antibody to band 3 synthetic peptide pep-COOH, detected a triplet in the 60-70 kDa range in brains from patients with AD but not from age-matched controls (FIGS. 10A and 10B).…”

Section: Senescent Cell Antigen and Anti-band 3 Antibodies In Diseasesmentioning

confidence: 99%

Immunoregulation of Cellular Life Span

Kay

2005

Annals of the New York Academy of Sciences

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Our current studies focus on the molecular changes induced by aging. During aging, changes in proteins occur that alter their function and render them immunogenic. These "neoantigens" are recognized by physiologic autoantibodies. Physiologic autoantibodies and their corresponding antigens offer therapeutic strategies for disease intervention through the innate immune response. Early studies done in the 1970s showed humans and animals to have physiologic antibodies that bind to a neoantigen called senescent cell antigen (SCA), which appears on senescent and damaged cells and initiates their removal by macrophages. These studies led to the discovery that oxidation can generate a new antigen in situ. Oxidation accelerated aging of red cells, generated SCA and IgG binding, and triggered removal of red cells by macrophages. Since then, a number of laboratories have found that oxidation can generate other neoantigens. For example, oxidized LDL (OxLDL) induces antibodies that can modify the natural progression of atherosclerosis. Apoptotic cells express oxidatively modified moieties on their surfaces that are involved in macrophage recognition and phagocytosis. Physiologic autoantibodies were used to isolate SCA from brain tissue. HPLC and fast atom bombardment ionization mass spectrometry (FAB-MS) of the isolated antigen suggested that the aging antigen is a subset of band 3, a family of proteins also called anion exchange proteins (AE1-3). FAB-MS results indicate that residues matching all three band 3 isoforms (AE1, AE2, and AE3) are detected in aging antigen fractions. Among the fragments identified with FAB-MS was a sequence corresponding to an aging epitope, human band 3 sequence LFKPPKYHPDVPYVKR, residue 812-830 in AE1; HHPDVTYVK, residue 1144-1152 in AE2; or HHPEQPYVTK, residue 1135-1144 in AE3. A residue that is close to that region was identified in mouse AE1 ASGPGAAAQIQEVK, residue 762-775. The potential for altering the natural progression of diseases using select peptide-defined epitopes within or overlapping the aging antigenic site (547-553 and 824-829) is discussed using the innate immune response to band 3 in malaria as an example.

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“…If this is the case, we can examine the mechanisms of AD in a simpler, more accessible system, such as the erythrocyte, and apply the knowledge gained to neurons. Bosman has studied band 3 and altered immune recognition in AD extensive ly [74][75][76][77][78], and addresses this in another arti cle in this issue [113].…”

Section: Serum Autoantibodies To Brain Band 3 Synthetic Peptides O Fmentioning

confidence: 99%

Brain and Erythrocyte Anion Transporter Protein, Band 3, as a Marker for Alzheimer’s Disease: Structural Changes Detected by Electron Microscopy, Phosphorylation, and Antibodies

Kay

Goodman²

1997

Gerontology

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Band 3, a ubiquitous membrane transport, regulatory, and structural protein, is represented in brain by at least 4 isoforms. Bands 3 in brain performs the same functions as it does in erythrocytes (RBC). It is susceptible to oxidative damage, which, ultimately, terminates its life and that of the cell. We examined the changes band 3 undergoes in Alzheimer’s disease (AD) because our previous studies suggest that band 3 is a pivotal protein in neurological disease. Because we hypothesize that AD is a total body disease, we examined peripheral blood cells as well as brain tissue to determine whether the same changes occur in both. Our results indicate that posttranslational changes occur in RBC band 3 that parallel changes in brain band 3. These include decreased ³²P-phosphate labeling in vitro of band 3 polypeptides in brain and RBC, increased degradation of band 3, alterations in band 3 recognized by polyclonal and monoclonal antibodies, and decreased anion and glucose transport by blood cells. Serum autoantibodies to band 3 peptides 588-602 and 822-839 were increased in AD patients compared to controls. These band 3 residues lie in anion transport/binding regions. This is consistent with alteration of this region in AD since it is recognized as antigenically different by the patients’ immune system. Our data support an immunological component to AD. The finding that changes in RBC in AD reflect those in brain and can be recognized by antibodies should facilitate development of blood tests for diagnosis and monitoring, and early therapy. It is anticipated that identification of molecular sites of posttranslational modification of band 3 will enable us to design specific preventive and treatment strategies, and target drugs to crucial molecular sites.

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Involvement of Neuronal Anion Exchange Proteins in Cell Death in Alzheimer's Disease

Cited by 13 publications

References 49 publications

Physiology of Microglia

Physiology of Microglia

Immunoregulation of Cellular Life Span

Brain and Erythrocyte Anion Transporter Protein, Band 3, as a Marker for Alzheimer’s Disease: Structural Changes Detected by Electron Microscopy, Phosphorylation, and Antibodies

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