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Neurobiology of Disease Presenilin-1 Regulates Neural Progenitor Cell Differentiation
 

Summary: Neurobiology of Disease
Presenilin-1 Regulates Neural Progenitor Cell Differentiation
in the Adult Brain
Archana Gadadhar,1 Robert Marr,2 and Orly Lazarov1
1Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, and 2Department of Neuroscience,
Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064
Presenilin-1 (PS1) is the catalytic core of the aspartyl protease -secretase. Previous genetic studies using germ-line deletion of PS1 and
conditional knock-out mice demonstrated that PS1 plays an essential role in neuronal differentiation during neural development, but it
remained unclear whether PS1 plays a similar role in neurogenesis in the adult brain. Here we show that neural progenitor cells infected
with lentiviral vectors-expressing short interfering RNA (siRNA) for the exclusive knockdown of PS1 in the neurogenic microenviron-
ments,exhibitadramaticenhancementofcelldifferentiation.Infectedcellsdifferentiatedintoneurons,astrocytesandoligodendrocytes,
suggesting that multipotentiality of neural progenitor cells is not affected by reduced levels of PS1. Neurosphere cultures treated with
-secretaseinhibitorsexhibitasimilarphenotypeofenhancedcelldifferentiation,suggestingthatPS1functioninneuralprogenitorcells
is -secretase-dependent. Neurospheres infected with lentiviral vectors expressing siRNA for the targeting of PS1 differentiated even in
the presence of the proliferation factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), suggesting that PS1
dominates EFG and bFGF signaling pathways. Reduction of PS1 expression in neural progenitor cells was accompanied by a decrease in
EGF receptor and -catenin expression level, suggesting that they are downstream essential transducers of PS1 signaling in adult neural
progenitor cells. These findings suggest a physiological role for PS1 in adult neurogenesis, and a potential target for the manipulation of
neural progenitor cell differentiation.
Introduction

  

Source: Alford, Simon - Department of Biological Sciences, University of Illinois at Chicago

 

Collections: Biology and Medicine