α2-macroglobulin attenuates β-amyloid peptide 1-40 fibril formation and associated neurotoxicity of cultured fetal rat cortical neurons

Yansheng Du, Kelly R. Bales, Richard C. Dodel, Xiaodong Liu, Michele A. Glinn, Jeffrey W. Horn, Sheila P. Little, Steven M. Paul

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

β-Amyloid peptides (Aβ) are deposited in an aggregated fibrillar form in both diffuse and senile plaques in the brains of patients with Alzheimer's disease. The neurotoxicity of Aβ in cultured neurons is dependent on its aggregation state, but the factors contributing to aggregation and fibril formation are poorly understood. In the present study, we investigated whether α2-macroglobulin (α2M), a protein present in neuritic plaques and elevated in Alzheimer's disease brain, is a potential regulatory factor for Aβ fibril formation. Previous studies in our laboratory have shown that α2M is an Aβ binding protein. We now report that, in contrast to another plaque-associated protein, α1-antichymotrypsin, α2M coincubated with Aβ significantly reduces aggregation and fibril formation in vitro. Additionally, cultured fetal rat cortical neurons are less vulnerable to the toxic actions of aged Aβ following pretreatment with α2M. We postulate that α2M is able to maintain Aβ in a soluble state, preventing fibril formation and associated neurotoxicity.

Original languageEnglish (US)
Pages (from-to)1182-1188
Number of pages7
JournalJournal of Neurochemistry
Volume70
Issue number3
StatePublished - Mar 1 1998

Keywords

  • α- Macroglobulin
  • β-Amyloid peptides
  • Alzheimer's disease
  • Neurotoxicity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Du, Y., Bales, K. R., Dodel, R. C., Liu, X., Glinn, M. A., Horn, J. W., Little, S. P., & Paul, S. M. (1998). α2-macroglobulin attenuates β-amyloid peptide 1-40 fibril formation and associated neurotoxicity of cultured fetal rat cortical neurons. Journal of Neurochemistry, 70(3), 1182-1188.