Gamma-Secretase: basic biology and therapeutic potential in Alzheimer’s disease
Event details
| Date | 09.12.2013 |
| Hour | 12:15 › 13:10 |
| Speaker | Prof. Patrick Fraering |
| Location | |
| Category | Conferences - Seminars |
Alzheimer’s disease (AD) is the most common form of dementia, for which no efficient treatment exists. Gamma-Secretase is a multi-subunit integral membrane protease complex that controls a wide variety of cellular and biological processes by regulating intramembrane proteolysis of proteins, including the Notch receptor and synaptic cell adhesion molecules. By catalyzing the final cleavage of the amyloid-beta precursor protein (APP), gamma-secretase is responsible for the neuronal production of the amyloid-beta peptides (A beta), the accumulation of which causes AD. As such, gamma-secretase has emerged as a key target to treat AD. Our group has developed new tools and systems that provided groundbreaking structural and functional insights into gamma-secretase and the intramembrane proteolysis of APP and A beta production. I will show how we used these to understand the genotype to phenotype conversion in early-onset familial AD caused by mutations in APP or in PS1, the catalytic subunit of gamma-secretase. Next, because clinical studies with gamma-secretase inhibitors (GSIs) have revealed severe side effects mainly attributed to impaired Notch signaling, we developed new strategies to selectively reduce A beta production without affecting other gamma-secretase functions. I will discuss the concepts, results and promises of our approaches, including small molecule gamma-secretase modulators (GSMs), APP-substrate neutralizing monoclonal antibodies, and the identification of new endogenous modulators of gamma-secretase. Together, our findings greatly contribute to efforts aiming at solving a major medical and socio-economic problem.
Practical information
- General public
- Free
Organizer
- SV Faculty
Contact
- Dr H. Hirling, M. Mary