17908039

Source:http://linkedlifedata.com/resource/pubmed/id/17908039

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0002395, umls-concept:C0033213, umls-concept:C0872278, umls-concept:C1706387
pubmed:issue	4
pubmed:dateCreated	2007-10-2
pubmed:abstractText	We have demonstrated that aged animals show significant improvements in cognitive function and neurogenesis after brain transplantation of human neural stem cells or of human adult mesenchymal stem cells that have been dedifferentiated by transfection of the embryonic stem cell gene. We have also demonstrated that peripheral administration of a pyrimidine derivative increased cognition, endogenous brain stem cell proliferation and neurogenesis. These results indicate a bright future for stem cell therapies in Alzheimer's disease (AD). Before this is realized, however, we need to consider the affect of AD pathology on stem cell biology to establish an effective stem cell therapy for this disease. Although amyloid-beta (Abeta) deposition is a hallmark of AD, an absence of a phenotype in the beta-amyloid precursor protein (APP) knockout mouse, might lead one to underestimate the potential physiological functions of APP and suggest that it is unessential or can be compensated for. We have found, however, that APP is needed for differentiation of neural stem cells (NSCs) in vitro, and that NSCs transplanted into a APP-knockout mouse did not migrate or differentiate -- indicating that APP plays an important role in differentiation or migration process of NSCs in the brain. Then again, treatment with high a concentration of APP or its over-expression increased glial differentiation of NSCs. Human NSCs transplanted into APP-transgenic mouse brain exhibited less neurogenesis and active gliosis around the plaque like formations. Treatment of such animals with the compound, (+)-phenserine, that is known to reduce APP protein levels, increased neurogenesis and suppressed gliosis. These results suggest APP levels can regulate NSC biology in the adult brain, that altered APP metabolism in Down syndrome or AD may have implications for the pathophysiology of these diseases, and that a combination of stem cell therapy and regulation of APP levels could provide a treatment strategy for these disorders.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/R01 AG23472
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/101208441
pubmed:citationSubset	IM
pubmed:status	MEDLINE
pubmed:month	Sep
pubmed:issn	1567-2050
pubmed:author	pubmed-author:ChoumrinaEE, pubmed-author:GreigN HNH, pubmed-author:KwakY DYD, pubmed-author:MarutleAA, pubmed-author:OhmitsuOO, pubmed-author:SugayaKK
pubmed:issnType	Print
pubmed:volume	4
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	370-7
pubmed:meshHeading	pubmed-meshheading:17908039-Alzheimer Disease, pubmed-meshheading:17908039-Animals, pubmed-meshheading:17908039-Gene Therapy, pubmed-meshheading:17908039-Humans, pubmed-meshheading:17908039-Stem Cell Transplantation, pubmed-meshheading:17908039-Stem Cells
pubmed:year	2007
pubmed:articleTitle	Practical issues in stem cell therapy for Alzheimer's disease.
pubmed:affiliation	Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL 32816. USA. ksugaya@mail.ucf.edu
pubmed:publicationType	Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural