Abstract
The remediation of neurodegeneration and cognitive decline in Alzheimers Disease (AD) remains a challenge to basic scientists and clinicians. It has been suggested that adult bone marrow stem cells can transdifferentiate into different neuronal phenotypes. Here we demonstrate that the a-secretase-cleaved fragment of the amyloid precursor protein (sAPP), a potent neurotrophic factor, potentiates the nerve growth factor (NGF)/retinoic acid (RA) induced transdifferentiation of bone marrow-derived adult progenitor cells (MAPCs) into neural progenitor cells and, more specifically, enhances their terminal differentiation into a cholinergic-like neuronal phenotype. The addition of sAPPa to NGF/RAstimulated MAPCs resulted in their conversion to neuronal-like cells as evidenced by the extension of neurites and the appearance of immature synaptic complexes. MAPCs differentiated in the presence of sAPPα and NGF/RA exhibited a 40% to as much as 75% increase in neuronal proteins including NeuN, β;-tubulin III, NFM, and synaptophysin, compared to MAPCs differentiated by NGF/RA alone. This process was accompanied by an increase in the levels of choline acetyltransferase, a marker of cholinergic neurons, compared to those of GABAergic and dopaminergic neuronal subtypes. MAPCs immunpositive for sAPP were identified within the septohippocampal system of transgenic PS/APP mice injected intravenously with sAPPa-transfected MAPCs and found in close proximity to the cerebral vasculature. Given that in AD cholinergic neurons are severely vulnerable to neurodegeneration and that the levels of sAPPa are significantly reduced, these findings suggest the combined use of sAPPα and MAPCs offers a new and potentially powerful therapeutic strategy for AD treatment.
Keywords: Adult stem cells, sAPPa, Alzheimer's disease, transdifferentiation, neurodegeneration, cholinergic neurons, trophic factors, animal models
Current Alzheimer Research
Title: sAPP Enhances the Transdifferentiation of Adult Bone Marrow Progenitor Cells to Neuronal Phenotypes
Volume: 3 Issue: 1
Author(s): Chun-Wei D. Chen, Rene M. Boiteau, Wen-Fu T. Lai, Steven W. Barger and Anne M. Cataldo
Affiliation:
Keywords: Adult stem cells, sAPPa, Alzheimer's disease, transdifferentiation, neurodegeneration, cholinergic neurons, trophic factors, animal models
Abstract: The remediation of neurodegeneration and cognitive decline in Alzheimers Disease (AD) remains a challenge to basic scientists and clinicians. It has been suggested that adult bone marrow stem cells can transdifferentiate into different neuronal phenotypes. Here we demonstrate that the a-secretase-cleaved fragment of the amyloid precursor protein (sAPP), a potent neurotrophic factor, potentiates the nerve growth factor (NGF)/retinoic acid (RA) induced transdifferentiation of bone marrow-derived adult progenitor cells (MAPCs) into neural progenitor cells and, more specifically, enhances their terminal differentiation into a cholinergic-like neuronal phenotype. The addition of sAPPa to NGF/RAstimulated MAPCs resulted in their conversion to neuronal-like cells as evidenced by the extension of neurites and the appearance of immature synaptic complexes. MAPCs differentiated in the presence of sAPPα and NGF/RA exhibited a 40% to as much as 75% increase in neuronal proteins including NeuN, β;-tubulin III, NFM, and synaptophysin, compared to MAPCs differentiated by NGF/RA alone. This process was accompanied by an increase in the levels of choline acetyltransferase, a marker of cholinergic neurons, compared to those of GABAergic and dopaminergic neuronal subtypes. MAPCs immunpositive for sAPP were identified within the septohippocampal system of transgenic PS/APP mice injected intravenously with sAPPa-transfected MAPCs and found in close proximity to the cerebral vasculature. Given that in AD cholinergic neurons are severely vulnerable to neurodegeneration and that the levels of sAPPa are significantly reduced, these findings suggest the combined use of sAPPα and MAPCs offers a new and potentially powerful therapeutic strategy for AD treatment.
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Chen D. Chun-Wei, Boiteau M. Rene, Lai T. Wen-Fu, Barger W. Steven and Cataldo M. Anne, sAPP Enhances the Transdifferentiation of Adult Bone Marrow Progenitor Cells to Neuronal Phenotypes, Current Alzheimer Research 2006; 3 (1) . https://dx.doi.org/10.2174/156720506775697205
DOI https://dx.doi.org/10.2174/156720506775697205 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
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Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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