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bioRxiv · 10.1101/424838

An Amyloid beta-derived Septapeptide has hMCP-1 Chemokine Activity

Vanalstyne, D.
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Abstract

Septapeptides (\"septas\"), previously identified as meningitis-specific antigens, defined by a rubella virus (RV) monoclonal antibody, were found in human Monocyte Chemoattractant Protein (hMCP-1) and on the surface of meningitis-causing bacteria, viruses and spirochetes. Some bacterial septas were tested for Ca+2 mobilization through receptor-associated heterotrimeric G-protein binding on THP-1 cells, progenitor cells of circulating peripheral macrophages. Certain of the free septas acted on their own as mild agonist of Ca+2 mobilization. Their signal transduction activity may be mediated through a single, or a single class, of receptor, but the data do not link this with the MCP-1 receptor on THP-1 cells. These data support the proposals that (1) the septas represent muteins of the MCP-1 active site for stem cell activation to macrophages and (2) infectious organisms may conserve and employ these sequences in order to facilitate their transport through the Blood Brain Barrier (BBB) to infect the Central Nervous System (CNS). Other MCP muteins have since been identified in the Alzheimers Disease (AD)-associated agents, amyloid beta (Abeta) and prions, as well as in viruses like HIV, known to establish chronic infections in the CNS. Rat glial progenitor cells in tissue culture were used to test for hMCP-1 activity in septas derived from amyloid beta. Nanomolar concentrations of the amyloid beta septa 13HHQKLVF19 were found to transform more than 60% of the progenitor cells into microglia in tissue culture. Taken together, these data support the hypothesis that amyloid beta may accumulate to increase the number of microglia available to combat chronic infection in the CNS. A new paradigm for neurodegenerative disease is presented.

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Vanalstyne, D.. 2018-09-23. An Amyloid beta-derived Septapeptide has hMCP-1 Chemokine Activity. https://doi.org/10.1101/424838

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