Amyloid β oligomerization is induced by brain lipid rafts

Sang Il Kim, Jae Sung Yi, Young-Gyu Ko

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Detergent-resistant lipid rafts are required for the generation of Aβ as they concentrate not only amyloid precursor protein (APP), but also the β- and γ-secretase that convert APP to Aβ. Recently, Aβ has been shown to be oligomerized, which results in neuronal cytotoxicity and synaptic failure. In this study, we have demonstrated that Aβ oligomers appeared immediately after the incubation of Aβ with lipid rafts isolated from the brain tissues of rats, and were converted into few Aβ fibrils, even after longer periods of incubation. The oligomerization of Aβ was not abolished after the brain lipid rafts were treated with heat, or with protease K, implying that the lipid raft proteins were determined not to be prerequisites for Aβ oligomerization. The cholesterol present in the lipid rafts might not be essential to Aβ oligomerization because Aβ oligomerization was not prevented after the cholesterol was removed from the lipid rafts with methyl-β-cyclodextrin (MβCD). The Aβ oligomerization was accelerated by the application of lipid rafts isolated from ganglioside-rich cells, C 2C 12 cells, whereas this was not observed with the lipid rafts isolated from ganglioside-poor eel Is SK-N-MC and HeLa cells. In addition, lipid raft-induced Aβ oligomerization was shown to be inhibited in CHO-K1 cells which were defective with regard to ganglioside biosynthesis. This indicates that Aβ oligomerization requires gangliosides that are enriched in the lipid rafts.

Original languageEnglish
Pages (from-to)878-889
Number of pages12
JournalJournal of Cellular Biochemistry
Volume99
Issue number3
DOIs
Publication statusPublished - 2006 Oct 15

Fingerprint

Oligomerization
Amyloid
Brain
Lipids
Gangliosides
Cholesterol
Eels
Endopeptidase K
Amyloid Precursor Protein Secretases
CHO Cells
Amyloid beta-Protein Precursor
Biosynthesis
Cyclodextrins
Cytotoxicity
HeLa Cells
Oligomers
Detergents
Rats
Hot Temperature
Tissue

Keywords

  • Amyloid β
  • Ganglioside
  • Lipid rafts

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Amyloid β oligomerization is induced by brain lipid rafts. / Kim, Sang Il; Yi, Jae Sung; Ko, Young-Gyu.

In: Journal of Cellular Biochemistry, Vol. 99, No. 3, 15.10.2006, p. 878-889.

Research output: Contribution to journalArticle

Kim, Sang Il ; Yi, Jae Sung ; Ko, Young-Gyu. / Amyloid β oligomerization is induced by brain lipid rafts. In: Journal of Cellular Biochemistry. 2006 ; Vol. 99, No. 3. pp. 878-889.
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