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Friday, February 23 • 8:00am - 12:00pm
293 C1 Complement mediates human cord blood serum derived APP α-secretase cleavage activity in vitro

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Allen Fan, Catherine Wang, Ahsan Habib, Darrell Sawmiller, Huayan Hou, Manasa Kanithi, Dan Zi, Zhi-Xu He, Paul R. Sanberg and Jun Tan

Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. In healthy individual amyloid precursor protein (APP) is cleaved by α-secretase generating sAPPα, which serve neuroprotective functions. However, in the neurodegenerative environment of AD patients, Aß peptides of either 40 or 42 residues are generated by increased beta and gamma secretase activity.  These proteins amalgamate in specific regions of the brains causing impairment and dysfunction characteristic of the disease. Human umbilical cord blood cells have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases.  Our most recent work studied the impact of umbilical cord blood serum (CBS) on modulation of sAPPα production. Heat-activated umbilical cord blood serum, (CBS) has significantly promoted sAPPα production indicating presence of heat sensitive α-secretase in CBS.  LC-MS/MS analysis was used to determine the molecular source of a-secretase in purified CBS and AgBS. Of the proteins identified, the subunits of C1 complex (C1q, C1r and C1s) and alpha-2-macroglobulin showed significantly greater levels in aCBSF compared with AgBSF.  Specifically, C1 markedly increased sAPPa  and aCTF production in a dose-dependent fashion, whereas C1q alone only minimally increased and C3 did not increase sAPPa production in the absence of sera.  Furthermore, C1q markedly increased sAPPa and aCTF, while decreasing Ab, in CHO/APPwt cells cultured in the presence of whole sera. These results confirm that APP a-secretase activity in human blood serum is mediated by C1 opening a potential modality of therapeutic for the future of AD.

Presenters
AF

Anran Fan

Post Doc, Morsani College of Medicine


Friday February 23, 2018 8:00am - 12:00pm
Ballroom