Amyloid beta-Peptide 1-42 Modulates the Proliferation of Mouse Neural Stem Cells: Upregulation of Fucosyltransferase IX and Notch Signaling

作者：Itokazu Yutaka; Yu Robert K^*

来源：Molecular Neurobiology, 2014, 50(1): 186-196.

DOI：10.1007/s12035-014-8634-8

• Alzheimer's disease
• Amyloid beta-peptide
• Glycosyltransferase
• Glycogene
• Neural stem cell
• Cell proliferation

Amyloid beta-peptides (A beta s) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer's disease (AD). A beta s 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 A beta s (A beta 1-40, A beta 1-42, and A beta 25-35) on NSC proliferation. Treatment of NSCs with A beta 1-42 significantly increased the number of those cells (149 +/- 10 %). This was not observed with A beta 1-40 which did not have any effects on the proliferative property of NSC. A beta 25-35, 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 A beta s on a number of key glycoconjugate metabolizing enzymes. Significantly, we found for the first time that A beta 1-42 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. A beta 1-42 also stimulated the Notch1 intracellular domain (NICD) by upregulation of the expression of Musashi-1 and the paired box protein, Pax6. Thus, A beta 1-42 upregulates NSC proliferation by modulating the expression of several glycogenes involved in Notch signaling.

• 出版日期2014-8