Journal article
Differential Processing of Amyloid-β Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells
The Journal of biological chemistry, Vol.284(35), pp.23806-23817
06/19/2009
DOI: 10.1074/jbc.M109.026328
PMCID: PMC2749153
PMID: 19542221
Abstract
The amyloid-β precursor protein (AβPP) is a ubiquitously expressed transmembrane protein whose cleavage product, the amyloid-β (Aβ) protein, is deposited in amyloid plaques in neurodegenerative conditions such as Alzheimer disease, Down syndrome, and head injury. We recently reported that this protein, normally associated with neurodegenerative conditions, is expressed by human embryonic stem cells (hESCs). We now report that the differential processing of AβPP via secretase enzymes regulates the proliferation and differentiation of hESCs. hESCs endogenously produce amyloid-β, which when added exogenously in soluble and fibrillar forms but not oligomeric forms markedly increased hESC proliferation. The inhibition of AβPP cleavage by β-secretase inhibitors significantly suppressed hESC proliferation and promoted nestin expression, an early marker of neural precursor cell (NPC) formation. The induction of NPC differentiation via the non-amyloidogenic pathway was confirmed by the addition of secreted AβPPα, which suppressed hESC proliferation and promoted the formation of NPCs. Together these data suggest that differential processing of AβPP is normally required for embryonic neurogenesis.
Details
- Title: Subtitle
- Differential Processing of Amyloid-β Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells
- Creators
- Prashob Porayette - Geriatric Research Education and Clinical CenterMiguel J. Gallego - Geriatric Research Education and Clinical CenterMaria M. Kaltcheva - Geriatric Research Education and Clinical CenterRichard L. Bowen - OTB Research, Raleigh, North Carolina 27615Sivan Vadakkadath Meethal - Geriatric Research Education and Clinical CenterCraig S. Atwood - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.284(35), pp.23806-23817
- DOI
- 10.1074/jbc.M109.026328
- PMID
- 19542221
- PMCID
- PMC2749153
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology
- Language
- English
- Date published
- 06/19/2009
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984353932902771
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