Peptides representing common epitopec sites for AD-associated agents, have hMCP-1 activity

Identification: Van Alstyne, Diane


Description

Peptides representing common epitopic sites for AD-associated agents, have hMCP-1 activity
 
Diane VanAlstyne
Septa Therapeutics Inc., Penticton, BC
 
Septapeptides (“septas”), previously identified as meningitis-specific antigens, defined by a rubella virus monoclonal antibody, were found in human Monocyte Chemoattractant Protein (hMCP-1) and on the surface of meningitis-causing bacteria, viruses and spirochetes.1-3    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 agonists 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 notion that (1) infectious organisms may conserve and employ these sequences in order to facilitate their transport through the BBB to infect the CNS and (2) the hypothesis that the septas represent muteins of the MCP-1 active site for monocyte stem cell activation to macrophages. Other MCP muteins have since been identified in the AD-associated agents, amyloid beta and prions, as well as in viruses like HIV, known to establish chronic infections in the CNS.  The amyloid beta septa 13HHQKLVF19 has been shown to transform rat glial progenitor cells into mature microglia/astrocytes in tissue culture4.  These data support the hypothesis that an AD-associated septa may serve to activate stem cells to increase the number of microglia available to combat chronic infection in the CNS.
 
1VanAlstyne & Sharma, US Patent No. 5,556,757
2VanAlstyne & Sharma, US Patent No. 5,510,264
3Van Alstyne & Sharma, US Patent No. 8,071,102
4Van Alstyne,  Jan. 4, 2018.  US Patent Application 62/613,621
                      

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