Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Sacha McElligott - New York University
Co-Author(s): Geoffrey Pires, NYU School of Medicine, New York, NY; Eleanor Drummond, NYU School of Medicine, New York, NY; Thomas Wisniewski, NYU School of Medicine, New York, NY
Amyloid plaques and neurofibrillary tangles (NFTs) are the two pathological hallmarks that define Alzheimer’s disease (AD). Recently, our team completed the most comprehensive analysis of the plaque proteome to date, and revealed a variety of novel proteins which had never before been implicated in the disease. Among these, Secernin-1 (SCRN1) exhibited consistently high expression in amyloid plaques. SCRN1 has been primarily identified as a cytosolic protein that regulates mast cells. Previous studies have also suggested that misregulation of SCRN1 may have a contributing role in a variety of cancers, as well as schizophrenia and bipolar disorder. However, very few studies have associated SCRN1 with AD, and a definitive role of SCRN1 in AD pathology remains elusive. Here, we used fluorescent immunohistochemistry on hippocampal sections from formalin-fixed paraffin-embedded, AD brain tissue, to show that SCRN1 colocalizes with phosphorylated Tau (pTau), present in both NFTs and dystrophic neurites. We compared these results to identically treated tissue from non-demented controls, which showed ubiquitous, yet low, levels of SCRN1. Surprisingly, SCRN1 staining also demonstrated variation across brain regions and across individuals, suggesting a possible occurrence of SCRN1 distribution in AD pathology. More recent efforts have further characterized patterning between SCRN1 and different pTau antibodies, each of which has selective affinity for various residues of pTau. Our results showed that SCRN1 consistently colocalized with PHF1–which is a monoclonal antibody that targets specific pTau serine residues–in NFTs, and less consistently with others, thus providing insight into the specific conformation of pTau that overlaps with SCRN1. Overall, the preliminary data generated from this study imply a potential relationship between SCRN1, pTau and cognitive impairment. Future research will include investigation of interactions at the molecular level between SCRN1 and pTau. References: Way et al. (2002) Purification and Identification of Secernin, a Novel Cytosolic Protein that Regulates Exocytosis in Mast Cells Mol. Biol. Cell, 13, 3344. Lin et al. (2015) Secernin-1 Contributes to Colon Cancer Progression through Enhancing Matrix Metalloproteinase-2/9 Exocytosis Disease Markers. Miyoshi et al. (2010) SCRN1 is a novel marker for prognosis in colorectal cancer W.J.S.O., 7(12). Drummond et al. (2017) Proteomic Differences in Amyloid Plaques in Rapidly Progressive and Sporadic Alzheimer’s Disease Acta Neuropathol.Not Submitted
Funder Acknowledgement(s): I extend the deepest gratitude to my peers and mentors during this process, namely Geoffrey Pires and Eleanor Drummond, whose daily insights and guidance helped sculpt both the project and my experience as an undergraduate researcher. Funding was primarily provided by the NIH Grant # 5R25NS080686 - 07, as part of the BP-ENDURE Fellowship, to which I am deeply grateful. Finally, I thank NYU for selecting me as a recipient of the Dean?s Undergraduate Research Fund, which has twice alleviated the financial burdens of my research.
Faculty Advisor: Eleanor Drummond, Eleanor.Drummond@nyumc.org
Role: With the oversight of my mentors, I conducted fluorescent immunohistochemistry stainings on all tissues, and conducted data analysis in conjunction with Geoffrey Pires. The design of my poster was my own, with feedback from Eleanor Drummond and Geoffrey Pires.