Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: Relationship to S-100B levels and blood–brain barrier function

Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

“…[5][6][7][8]25 Endogenous Ab-binding proteins have been shown to (1) sequester Ab, resulting in an increase in the fraction of bound Ab and a decrease in the level of free Ab, (2) inhibit the aggregation and polymerization of Ab, thus preventing amyloid plaque formation, and (3) suppress Ab-induced cytotoxicity. [5][6][7][8] DBP is an abundant protein in both plasma and CSF, 10,11,34 and our results show that, similar to other known circulating proteins that sequester Ab, secretory DBP binds to Ab and reduces Ab-mediated pathology. We have therefore discovered a novel endogenous Ab-binding protein with therapeutic potential.…”

“…As many Ab-binding proteins, such as TTR, apoE, apoJ, and apoA1, are known to accumulate with Ab in amyloid No Ab bands were detected in the littermate mice; n ¼ 4 each cases deposits 5,17 and the level of DBP in CSF is increased in AD patients, 11,15,16 we examined whether DBP is present in the amyloid plaques of brains from AD patients and transgenic animal model of AD. We double-stained human AD and control brain with antibodies against Ab (4G8) and DBP.…”

“…Although the level of DBP in CSF has been known to be increased in AD patients, and several lines of evidence have suggested that DBP plays a role in AD, 11,15,16,32 there is no direct evidence of whether or how DBP affects AD-related pathology. Our data clearly show that DBP interacts directly with Ab and reduces the formation of aggregated Ab.…”

“…9 It is a secretory protein that has been detected in the plasma and CSF at markedly higher concentrations than its ligands. 10,11 The nomenclature of DBP has changed several times in the past six decades because of the different biological actions that it controls, and has been known as group-specific component globulin, DBP, and DBP-macrophage-activating factor. 12 DBP contains binding sites for several proteins and molecules, including vitamin D, C5a, actin, fatty acids, and endotoxin, suggesting that it is a multifunctional protein.…”

“…10,12,13 Many studies have reported that changes in DBP concentration are linked to the pathology of several diseases, including hepatic failure, diabetes, and multiple sclerosis. 10,[12][13][14] Recently, Gressner et al 11 reported that intrathecal synthesis of DBP is increased in patients with severe neurodegeneration, including AD, and suggested that upregulated DBP may act as an actin scavenger in neurodegenerative diseases. Several other studies also have shown that the level of DBP in CSF is increased in AD patients and suggested that this plays a role in the pathology of AD.…”