Amyloid β-Peptide 1–42 Modulates the Proliferation of Mouse Neural Stem Cells

Upregulation of Fucosyltransferase IX and Notch Signaling

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15 Citations (Scopus)

Abstract

Amyloid β-peptides (Aβs) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer’s disease (AD). Aβs are reported to possess proliferation effects on neural stem cells (NSCs); however, this effect remains controversial. Thus, clarification of their physiological function is an important topic. We have systematically evaluated the effects of several putative bioactive Aβs (Aβ1–40, Aβ1–42, and Aβ25–35) on NSC proliferation. Treatment of NSCs with Aβ1–42 significantly increased the number of those cells (149 ± 10 %). This was not observed with Aβ1–40 which did not have any effects on the proliferative property of NSC. Aβ25–35, on the other hand, exhibited inhibitory effects on cellular proliferation. Since cell surface glycoconjugates, such as glycolipids, glycoproteins, and proteoglycans, are known to be important for maintaining cell fate determination, including cellular proliferation, in NSCs and they undergo dramatic changes during differentiation, we examined the effect of Aβs on a number of key glycoconjugate metabolizing enzymes. Significantly, we found for the first time that Aβ1–42 altered the expression of several key glycosyltransferases and glycosidases, including fucosyltransferase IX (FUT9), sialyltransferase III (ST-III), glucosylceramide ceramidase (GLCC), and mitochondrial sialidase (Neu4). FUT9 is a key enzyme for the synthesis of the Lewis X carbohydrate epitope, which is known to be expressed in stem cells. Aβ1–42 also stimulated the Notch1 intracellular domain (NICD) by upregulation of the expression of Musashi-1 and the paired box protein, Pax6. Thus, Aβ1–42 upregulates NSC proliferation by modulating the expression of several glycogenes involved in Notch signaling.

Original languageEnglish (US)
Pages (from-to)186-196
Number of pages11
JournalMolecular Neurobiology
Volume50
Issue number1
DOIs
StatePublished - Oct 2 2014

Fingerprint

Fucosyltransferases
Neural Stem Cells
Amyloid
Up-Regulation
Peptides
Cell Proliferation
Glycoconjugates
Amyloid Plaques
Ceramidases
Sialyltransferases
Glucosylceramides
Glycosyltransferases
Glycoside Hydrolases
Glycolipids
Neuraminidase
Proteoglycans
Enzymes
Epitopes
Glycoproteins
Alzheimer Disease

Keywords

  • Alzheimer’s disease
  • Amyloid β-peptide
  • Cell proliferation
  • Glycogene
  • Glycosyltransferase
  • Neural stem cell

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

@article{d7f2d70cd5a14674b0cd82eb26effeaa,
title = "Amyloid β-Peptide 1–42 Modulates the Proliferation of Mouse Neural Stem Cells: Upregulation of Fucosyltransferase IX and Notch Signaling",
abstract = "Amyloid β-peptides (Aβs) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer’s disease (AD). Aβs are reported to possess proliferation effects on neural stem cells (NSCs); however, this effect remains controversial. Thus, clarification of their physiological function is an important topic. We have systematically evaluated the effects of several putative bioactive Aβs (Aβ1–40, Aβ1–42, and Aβ25–35) on NSC proliferation. Treatment of NSCs with Aβ1–42 significantly increased the number of those cells (149 ± 10 {\%}). This was not observed with Aβ1–40 which did not have any effects on the proliferative property of NSC. Aβ25–35, on the other hand, exhibited inhibitory effects on cellular proliferation. Since cell surface glycoconjugates, such as glycolipids, glycoproteins, and proteoglycans, are known to be important for maintaining cell fate determination, including cellular proliferation, in NSCs and they undergo dramatic changes during differentiation, we examined the effect of Aβs on a number of key glycoconjugate metabolizing enzymes. Significantly, we found for the first time that Aβ1–42 altered the expression of several key glycosyltransferases and glycosidases, including fucosyltransferase IX (FUT9), sialyltransferase III (ST-III), glucosylceramide ceramidase (GLCC), and mitochondrial sialidase (Neu4). FUT9 is a key enzyme for the synthesis of the Lewis X carbohydrate epitope, which is known to be expressed in stem cells. Aβ1–42 also stimulated the Notch1 intracellular domain (NICD) by upregulation of the expression of Musashi-1 and the paired box protein, Pax6. Thus, Aβ1–42 upregulates NSC proliferation by modulating the expression of several glycogenes involved in Notch signaling.",
keywords = "Alzheimer’s disease, Amyloid β-peptide, Cell proliferation, Glycogene, Glycosyltransferase, Neural stem cell",
author = "Yutaka Itokazu and Yu, {Robert K}",
year = "2014",
month = "10",
day = "2",
doi = "10.1007/s12035-014-8634-8",
language = "English (US)",
volume = "50",
pages = "186--196",
journal = "Molecular Neurobiology",
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T1 - Amyloid β-Peptide 1–42 Modulates the Proliferation of Mouse Neural Stem Cells

T2 - Upregulation of Fucosyltransferase IX and Notch Signaling

AU - Itokazu, Yutaka

AU - Yu, Robert K

PY - 2014/10/2

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N2 - Amyloid β-peptides (Aβs) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer’s disease (AD). Aβs are reported to possess proliferation effects on neural stem cells (NSCs); however, this effect remains controversial. Thus, clarification of their physiological function is an important topic. We have systematically evaluated the effects of several putative bioactive Aβs (Aβ1–40, Aβ1–42, and Aβ25–35) on NSC proliferation. Treatment of NSCs with Aβ1–42 significantly increased the number of those cells (149 ± 10 %). This was not observed with Aβ1–40 which did not have any effects on the proliferative property of NSC. Aβ25–35, on the other hand, exhibited inhibitory effects on cellular proliferation. Since cell surface glycoconjugates, such as glycolipids, glycoproteins, and proteoglycans, are known to be important for maintaining cell fate determination, including cellular proliferation, in NSCs and they undergo dramatic changes during differentiation, we examined the effect of Aβs on a number of key glycoconjugate metabolizing enzymes. Significantly, we found for the first time that Aβ1–42 altered the expression of several key glycosyltransferases and glycosidases, including fucosyltransferase IX (FUT9), sialyltransferase III (ST-III), glucosylceramide ceramidase (GLCC), and mitochondrial sialidase (Neu4). FUT9 is a key enzyme for the synthesis of the Lewis X carbohydrate epitope, which is known to be expressed in stem cells. Aβ1–42 also stimulated the Notch1 intracellular domain (NICD) by upregulation of the expression of Musashi-1 and the paired box protein, Pax6. Thus, Aβ1–42 upregulates NSC proliferation by modulating the expression of several glycogenes involved in Notch signaling.

AB - Amyloid β-peptides (Aβs) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer’s disease (AD). Aβs are reported to possess proliferation effects on neural stem cells (NSCs); however, this effect remains controversial. Thus, clarification of their physiological function is an important topic. We have systematically evaluated the effects of several putative bioactive Aβs (Aβ1–40, Aβ1–42, and Aβ25–35) on NSC proliferation. Treatment of NSCs with Aβ1–42 significantly increased the number of those cells (149 ± 10 %). This was not observed with Aβ1–40 which did not have any effects on the proliferative property of NSC. Aβ25–35, on the other hand, exhibited inhibitory effects on cellular proliferation. Since cell surface glycoconjugates, such as glycolipids, glycoproteins, and proteoglycans, are known to be important for maintaining cell fate determination, including cellular proliferation, in NSCs and they undergo dramatic changes during differentiation, we examined the effect of Aβs on a number of key glycoconjugate metabolizing enzymes. Significantly, we found for the first time that Aβ1–42 altered the expression of several key glycosyltransferases and glycosidases, including fucosyltransferase IX (FUT9), sialyltransferase III (ST-III), glucosylceramide ceramidase (GLCC), and mitochondrial sialidase (Neu4). FUT9 is a key enzyme for the synthesis of the Lewis X carbohydrate epitope, which is known to be expressed in stem cells. Aβ1–42 also stimulated the Notch1 intracellular domain (NICD) by upregulation of the expression of Musashi-1 and the paired box protein, Pax6. Thus, Aβ1–42 upregulates NSC proliferation by modulating the expression of several glycogenes involved in Notch signaling.

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KW - Glycogene

KW - Glycosyltransferase

KW - Neural stem cell

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