Alpha1-antichymotrypsin/Alzheimer's peptide Abeta(1-42) complex perturbs lipid metabolism and activates transcription factors PPARgamma and NFkappaB in human neuroblastoma (Kelly) cells.

Research output: Contribution to journalArticle


Amyloid-beta peptide (A) and the serpin proteinase inhibitor 1-antichymotrypsin (ACT) are components of the amyloid plaques associated with Alzheimer's disease (AD). A exists in soluble monomeric and oligomeric forms and in an insoluble polymerised fibrillar form, but it is not clear which of these plays the most important role in the etiology of AD. In vitro, A1-42 interacts with ACT, and as a result of this, ACT loses its proteinase inhibitor activity and polymerisation of A1-42 is promoted. Here we provide evidence that new molecular forms resulting from incubation of ACT with A1-42 have multiple cellular level effects on neuronal cells. The mixture of soluble A and an ACT/A complex formed by 2 hr incubation at a 10:1 molar ratio of A:ACT strongly induce cellular proliferation and expression of transcription factors peroxisome proliferator-activated receptor-gamma (PPAR) and NFB, and also increase uptake and depress degradation of native and oxidised low-density lipoprotein (LDL) by cells. Similar but less pronounced effects are seen when cells are exposed to the A peptide alone preincubated for 2 hr. A1-42 and to a lesser extent ACT/A1-42 complex mixture prepared by 2 hr incubation both inhibit association of native LDL with cells. Neither ACT alone nor the A1-42 and ACT/A1-42 forms prepared by 24-hr incubation show any significant effects in these assays. We propose that specific molecular forms of A1-42 and ACT/A1-42 complex mixture, both dependent on the abundances of A1-42 and ACT/A1-42 in vivo and on their time of exposure to each other, have cellular effects which are important for the initiation and progression of the pathologies associated with AD.


Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences


  • Human, Lipids: metabolism, Lipoproteins, LDL: metabolism, NF-kappa B: drug effects, NF-kappa B: metabolism, Neuroblastoma, Neurons: enzymology, Neurons: pathology, Gene Expression Regulation: physiology, Brain: physiopathology, Cell Division: drug effects, Cell Division: physiology, Electrophoresis, Gene Expression Regulation: drug effects, Brain: enzymology, Binding Sites: drug effects, Binding Sites: physiology, Amyloid beta-Protein: metabolism, Amyloid beta-Protein: pharmacology, Alzheimer Disease: physiopathology, Alzheimer Disease: enzymology, LDL: drug effects, Oxidation-Reduction: drug effects, Peptide Fragments: metabolism, Peptide Fragments: pharmacology, Receptors, Cytoplasmic and Nuclear: drug effects, Cytoplasmic and Nuclear: metabolism, Senile Plaques: enzymology, Support, Non-U.S. Gov't, Transcription Factors: drug effects, Transcription Factors: metabolism, Transcription, Genetic: drug effects, Genetic: physiology, Tumor Cells, Cultured, alpha 1-Antichymotrypsin: metabolism, alpha 1-Antichymotrypsin: pharmacology
Original languageEnglish
Pages (from-to)511-522
JournalJournal of Neuroscience Research
Issue number4
Publication statusPublished - 2002
Publication categoryResearch