Amyloid β-protein affects cholesterol metabolism in cultured neurons: Implications for pivotal role of cholesterol in the amyloid cascade

Jian Sheng Gong, Naoya Sawamura, Kun Zou, Juro Sakai, Katsuhiko Yanagisawa, Makoto Michikawa*

*この研究の対応する著者

研究成果: Article査読

50 被引用数 (Scopus)

抄録

Recently, we have found that alterations in cellular cholesterol metabolism are involved in promotion of tau phosphorylation (Fan et al. [2001] J. Neurochem. 76: 391-400; Sawamura et al. [2001] J. Biol. Chem. 276:10314-10319). In addition, we have shown that amyloid β-protein (Aβ) promotes cholesterol release to form Aβ-lipid particles (Michikawa et al. [2001] J. Neurosci. 21:7226-7235). These lines of evidence inspired us to conduct further studies on whether Aβ affects cholesterol metabolism in neurons, which might lead to tau phosphorylation. Here, we report the effect of Aβ1-40 on cholesterol metabolism in cultured neurons prepared from rat cerebral cortex. Oligomeric Aβ1-40 inhibited cholesterol synthesis and reduced cellular cholesterol levels in a dose- and time-dependent manner, while freshly dissolved Aβ had no effect on cholesterol metabolism. However, oligomeric Aβ had no effect on the proteolysis of sterol regulatory element binding protein-2 (SREBP-2) or protein synthesis in cultured neurons. Oligomeric Aβ did not enhance lactate dehydrogenase (LDH) release from neuronal cells or decrease signals in the cultures reactive to 3,3′-Bis[N,N-bis(carboxymethyl)aminomethy]fluorescein, hexaacetoxymethyl ester (calcein AM) staining, indicating that A& used in this experiment did not cause neuronal death during the time course of our experiments. Since alterations in cholesterol metabolism induce tau phosphorylation, our findings that oligomeric A& alters cellular cholesterol homeostasis may provide new insight into the mechanism underlying the amyloid cascade hypothesis.

本文言語English
ページ(範囲)438-446
ページ数9
ジャーナルJournal of Neuroscience Research
70
3
DOI
出版ステータスPublished - 2002 11月 2
外部発表はい

ASJC Scopus subject areas

  • 細胞および分子神経科学

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