Volume 08
Journal of Alzheimers Disease & Parkinsonism
Alzheimer's Congress 2018
May 30-31, 2018
Page 12
Notes:
conference
series
.com
May 30-31, 2018 Osaka, Japan
10
th
World Congress on
Alzheimer's Disease & Dementia
Adult neurogenesis stimulation as an anti-alzheimer’s disease therapeutic approach
S
ox2 is a transcription factor that controls the balance between stem cells self-renewal and differentiation, thereby
contributing to the control of neurogenesis. Importantly, Sox2 deficiency triggers neurodegeneration in the adult brain.
Moreover, Sox2 co localizes with the Amyloid Precursor Protein (APP) in stem cells and Sox2 levels are decreased in the
brain of Alzheimer’s Disease (AD) patients. We have recently reported the existence of functional network engaging Sox2, the
APP Intracellular Domain AICD and the secretase ADAM10
in vitro
in human cells. Indeed, Sox2 is a potent activator of the
non-amyloidogenic processing of APP by increasing the expression of ADAM10. Secondly, transient overexpression of the
pro-apoptotic C-terminal APP-derived AICD50 metabolite reduces Sox2 transcription whereas inhibiting AICD production
with a -secretase inhibitor augments Sox2 expression, and consequently ADAM10 protein levels, in HEK293 and SH-SY5Y
cell lines. Experiments carried out
in vivo
indicate that Sox2 levels are diminished in the hippocampus of mouse models of AD
when compared to control animals. Whether ADAM10 and Sox2 co-localize in neurogenic areas of the adult mouse brain and
determining if this co-localization is impaired in transgenic AD models is currently under investigation. Finally, the impact
of the pharmacological or the genetic modulation of this network on the reprogramming of human induced pluripotent stem
cells into neurons is currently monitored in an
in vitro
model of neurogenesis. Altogether, our data suggest that enhancing the
Sox2/ADAM10 axis may favor neuroprotection and neurogenesis during the development of AD.
Biography
Bruno Vincent has completed his PhD from the University of Nice, France in 1996. He has then joined the Rockefeller University in New York as a Postdoctoral
Fellow. He returned back to France in 1999 at the Institute of Molecular and Cellular Pharmacology in Sophia-Antipolis and took the position of permanent
Researcher at the National Center for Scientific Research (CNRS) in 2001 and was promoted to Research Director. In 2010, he moved to Mahidol University
in Bangkok where his research team is working on the identification of new AD-regulating factors. He has published 60 articles in reputed international journals.
bruno.vin@mahidol.ac.thBruno Vincent
Mahidol University, Thailand
Bruno Vincent, J Alzheimers Dis Parkinsonism 2018, Volume 8
DOI: 10.4172/2161-0460-C4-044