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γ-Secretase Modulatory Proteins: The Guiding Hand Behind the Running Scissors

EVENT: 
Weekly Seminar | Not Open to the Public
Who Should Attend: 
Researchers

Abstract

γ-Secretase is a four subunit, 20-pass transmembrane enzyme that cleaves amyloid precursor protein, catalyzing the formation of amyloid beta peptides that form amyloid plaques, which contribute to Alzheimer’s disease pathogenesis. γ-Secretase also cleaves Notch and other more than 100 type I transmembrane substrates. Despite its seemingly promiscuous enzymatic capacity, γ-secretase activity is tightly regulated. This regulation is a function of many cellular entities, including but not limited to the essential γ-secretase subunits, nonessential (modulatory) subunits, and γ-secretase substrates. We will discuss how γ-secretase is regulated by modulatory proteins under hypoxia and neuroinflammation. A better understanding of these mechanisms will aid in the development of effective therapeutics for γ-secretase-associated diseases like Alzheimer’s disease and Notch-addicted cancer.

Dr. Yueming Li's Figure

Publications

Ji-Yeun Hur, Georgia R Frost, Xianzhong Wu, Christina Crump, Si Jia Pan, Eitan Wong, Marilia Barros, Thomas Li, Pengju Nie, Yujia Zhai, Jen Chyong Wang, Julia Tcw, Lei Guo, Andrew McKenzie, Chen Ming, Xianxiao Zhou, Minghui Wang, Yotam Sagi, Alan E Renton, Bianca T Esposito, Yong Kim, Katherine R Sadleir, Ivy Trinh, Robert A Rissman, Robert Vassar, Bin Zhang, Douglas S Johnson, Eliezer Masliah, Paul Greengard, Alison Goate, Yue-Ming Li
The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease
Nature. 2020 Oct;586(7831):735-740. doi: 10.1038/s41586-020-2681-2. Epub 2020 Sep 2.
Pengju Nie, Teja Kalidindi, Veronica L Nagle, Xianzhong Wu, Thomas Li, George P Liao, Georgia Frost, Kelly E Henry, Blesida Punzalan, Lukas M Carter, Jason S Lewis, Naga Vara Kishore Pillarsetty, Yue-Ming Li
Imaging of Cancer γ-Secretase Activity Using an Inhibitor-Based PET Probe
Clin Cancer Res. 2021 Nov 15;27(22):6145-6155. doi: 10.1158/1078-0432.CCR-21-0940. Epub 2021 Sep 2.
Jennifer C Villa, Danica Chiu, Alissa H Brandes, Freddy E Escorcia, Carlos H Villa, William F Maguire, Cheng-Jun Hu, Elisa de Stanchina, M Celeste Simon, Sangram S Sisodia, David A Scheinberg, Yue-Ming Li
Nontranscriptional role of Hif-1α in activation of γ-secretase and notch signaling in breast cancer
Cell Rep. 2014 Aug 21;8(4):1077-92. doi: 10.1016/j.celrep.2014.07.028. Epub 2014 Aug 14.

When

Tuesday, March 29, 2022 - 12:30pm

Where

Conference Room: 
Online Webinar

More Information

Darlene White

Conditions & Recovery

Neurodegenerative Diseases icon
Worldwide, 50 million people are living with Alzheimer's and other dementias.