Differential Processing of Amyloid-β Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells

• DOI: 10.1074/jbc.m109.026328
• Publication Date: 2009-06-20T02:13:54Z
• Authors: Prashob Porayette; Miguel J. Gallego; Maria M. Kaltcheva; Richard L. Bowen; Sivan Vadakkadath...; Craig S. Atwood
• Keywords: BACE1-AS; Amyloid beta; Nestin; Precursor cell; P3 peptide

The amyloid-beta precursor protein (AbetaPP) is a ubiquitously expressed transmembrane whose cleavage product, the (Abeta) protein, deposited in amyloid plaques neurodegenerative conditions such as Alzheimer disease, Down syndrome, and head injury. We recently reported that this normally associated with conditions, by human embryonic stem cells (hESCs). now report differential processing of AbetaPP via secretase enzymes regulates proliferation differentiation hESCs. hESCs endogenously produce amyloid-beta, which when added exogenously soluble fibrillar forms but not oligomeric markedly increased hESC proliferation. inhibition beta-secretase inhibitors significantly suppressed promoted nestin expression, an early marker neural cell (NPC) formation. induction NPC non-amyloidogenic pathway was confirmed addition secreted AbetaPPalpha, formation NPCs. Together these data suggest required for neurogenesis.