Abstract
Accumulation of beta-amyloid (Aβ) in the extracellular space, which is one of the hallmarks of Alzheimer’s disease (AD), depends on the balance between its synthesis and clearance. The physiological role of extracellular chaperones, capable of affecting early events in the amyloid cascade, is increasingly being investigated by many research groups. Among these proteins, we focused on haptoglobin, which we recently found to form a complex with beta-amyloid in brain tissues or cerebrospinal fluids from patients with AD. We also previously reported that haptoglobin increases with age in rat hippocampus. Major aim of this study was to evaluate whether haptoglobin influences Aβ interaction with astrocytes and its internalization into these cells. Haptoglobin effect on Aβ-induced cell death was also explored. We report here that haptoglobin impairs Aβ uptake by human glioblastoma–astrocytoma cell line U-87 MG and limits the toxicity of this peptide on these cells. Of note, our data also show that Aβ can stimulate haptoglobin release by astrocyte cell lines. The study of the risk of developing AD should be focused not only on the analysis of Aβ but also on the level of critical ligands, such as haptoglobin, able to influence peptide aggregation or clearance.
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Acknowledgments
This research was supported by a grant from the Compagnia di San Paolo (Neuroscience Program; 3868 SD/SD-2008.2487). The authors have no conflict of interests to declare.
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Maresca, B., Spagnuolo, M.S. & Cigliano, L. Haptoglobin Modulates Beta-Amyloid Uptake by U-87 MG Astrocyte Cell Line. J Mol Neurosci 56, 35–47 (2015). https://doi.org/10.1007/s12031-014-0465-6
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DOI: https://doi.org/10.1007/s12031-014-0465-6