Mutual stimulation of beta-amyloid fibrillogenesis by clioquinol and divalent metals.

Neuromolecular Medicine
Silvia BologninFernanda Ricchelli

Abstract

As reported by some authors, clioquinol (CQ), a 8-hydroxyquinoline derivative, has produced very encouraging results in the treatment of Alzheimer's disease (AD). Its biological effects are most likely ascribed to complexation of specific metal ions, such as copper (II) and zinc (II), critically associated with beta-amyloid (A beta) aggregation/fibrillogenesis and degeneration processes in the brain. The present study was aimed at assessing the in vitro effects of CQ on the aggregation/fibrillogenesis properties of human A beta either alone or complexed with Cu(2+) and Zn(2+). Surprisingly, our data indicated that CQ promoted rather than inhibited the formation of A beta fibrillar aggregates when added metal ions were present. To understand whether the latter effects were related to the peptide amino acid sequence, we also investigated the aggregational profile of rat A beta, which differs from the human homologous for three amino acidic substitutions. Such a sequence alteration drastically reduced the tendency of the peptide to undergo spontaneous aggregation/fibrillization. In the presence of CQ and metals, however, also rat A beta showed a strong propensity to generate fibrillar aggregates. In agreement with the pro-aggregat...Continue Reading

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Citations

Dec 1, 2009·Neuromolecular Medicine·Silvia BologninPaolo Zatta
May 1, 2009·Expert Review of Neurotherapeutics·Masahiro KawaharaYutaka Sadakane
Jun 23, 2009·Trends in Pharmacological Sciences·Paolo ZattaStefano L Sensi
Oct 12, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Martina G M WeibullLars Hemmingsen
Mar 19, 2020·Protein and Peptide Letters·Jia WangBaohua Zeng

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