Amyloid precursor protein regulates differentiation of human neural stem cells.
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Amyloid precursor protein regulates differentiation of human neural stem cells. / Kwak, Y-D; Brannen, C L; Qu, T; Kim, H M; Dong, X; Soba, Peter; Majumdar, A; Kaplan, A; Beyreuther, K; Sugaya, K.
In: STEM CELLS DEV, Vol. 15, No. 3, 3, 2006, p. 381-389.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Amyloid precursor protein regulates differentiation of human neural stem cells.
AU - Kwak, Y-D
AU - Brannen, C L
AU - Qu, T
AU - Kim, H M
AU - Dong, X
AU - Soba, Peter
AU - Majumdar, A
AU - Kaplan, A
AU - Beyreuther, K
AU - Sugaya, K
PY - 2006
Y1 - 2006
N2 - Although amyloid beta (Abeta) deposition has been a hallmark of Alzheimer's disease (AD), the absence of a phenotype in the beta amyloid precursor protein (APP) knockout mouse, tends to detract our attention away from the physiological functions of APP. Although much attention has been focused on the neurotoxicity of Abeta, many studies suggest the involvement of APP in neuroplasticity. We found that secreted amyloid precursor protein (sAPP) increased the differentiation of human neural stem cells (hNSCs) in vitro, while an antibody-recognizing APP dose-dependently inhibited these activities. With a high dose of sAPP treatment or wild-type APP gene transfection, hNSCs were differentiated into astrocytes rather than neurons. In vivo, hNSCs transplanted into APP-transgenic mouse brain exhibited glial differentiation rather than neural differentiation. Our results suggest that APP regulates neural stem cell biology in the adult brain, and that altered APP metabolism in Down syndrome or AD may have implications for the pathophysiology of these diseases.
AB - Although amyloid beta (Abeta) deposition has been a hallmark of Alzheimer's disease (AD), the absence of a phenotype in the beta amyloid precursor protein (APP) knockout mouse, tends to detract our attention away from the physiological functions of APP. Although much attention has been focused on the neurotoxicity of Abeta, many studies suggest the involvement of APP in neuroplasticity. We found that secreted amyloid precursor protein (sAPP) increased the differentiation of human neural stem cells (hNSCs) in vitro, while an antibody-recognizing APP dose-dependently inhibited these activities. With a high dose of sAPP treatment or wild-type APP gene transfection, hNSCs were differentiated into astrocytes rather than neurons. In vivo, hNSCs transplanted into APP-transgenic mouse brain exhibited glial differentiation rather than neural differentiation. Our results suggest that APP regulates neural stem cell biology in the adult brain, and that altered APP metabolism in Down syndrome or AD may have implications for the pathophysiology of these diseases.
KW - Animals
KW - Humans
KW - Male
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Apoptosis
KW - Gene Expression Regulation/drug effects
KW - Cell Differentiation/drug effects
KW - Neuroglia/cytology
KW - RNA, Messenger/genetics/metabolism
KW - Cell Movement/drug effects
KW - Amyloid beta-Protein Precursor/metabolism/pharmacology
KW - Cell Transplantation
KW - Neurons/cytology/drug effects
KW - Peptide Fragments/metabolism/pharmacology
KW - Stem Cells/cytology/drug effects
KW - Animals
KW - Humans
KW - Male
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Apoptosis
KW - Gene Expression Regulation/drug effects
KW - Cell Differentiation/drug effects
KW - Neuroglia/cytology
KW - RNA, Messenger/genetics/metabolism
KW - Cell Movement/drug effects
KW - Amyloid beta-Protein Precursor/metabolism/pharmacology
KW - Cell Transplantation
KW - Neurons/cytology/drug effects
KW - Peptide Fragments/metabolism/pharmacology
KW - Stem Cells/cytology/drug effects
M3 - SCORING: Journal article
VL - 15
SP - 381
EP - 389
JO - STEM CELLS DEV
JF - STEM CELLS DEV
SN - 1547-3287
IS - 3
M1 - 3
ER -
