Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration

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21 Citations (Scopus)

Abstract

Phosphorylated Amyloid-beta (Abeta) was identified in Alzheimer's disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Abeta phosphorylation. The phosphorylated Abeta peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils. Mutation of the serine 26 residue and inhibition of Abeta phosphorylation by the CDK-1 inhibitor olomoucine prevented Abeta toxicity, suggesting that the phosphorylated Abeta peptide represents a toxic intermediate. Cannabinoids prevented phosphorylated Abeta toxicity. The results from this study suggest that Abeta phosphorylation could play a role in AD pathology and represent a novel therapeutic target.

Original languageEnglish
Pages (from-to)381-402
Number of pages22
JournalSub-Cellular Biochemistry
Volume38
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Alzheimer Disease/pathology
  • Amyloid beta-Peptides/metabolism
  • Animals
  • Cyclin-Dependent Kinases/antagonists & inhibitors
  • Enzyme Inhibitors/therapeutic use
  • Humans
  • Kinetin
  • Nerve Degeneration/pathology
  • Phosphoproteins/antagonists & inhibitors
  • Phosphorylation
  • Purines/therapeutic use

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