Affiliations: [a] CNR-Institute for Biomedical Technologies, Padova Unit “Metalloproteins”, Italy | [b] Department of Biology, University of Padova, Italy | [c] Department of Pharmacological Sciences, University of Padova, Padova, Italy
Correspondence:
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Corresponding author: Paolo Zatta, Institute for Biomedical Technologies, Unit, “Metalloprotein”, Department of Biology, University of Padova, V.le G. Colombo, 3, 35121 Padova, Italy. Tel.: +39 049 8276331; Fax: +39 049 8276330; E-mail: zatta@mail.bio.unipd.it
Abstract: Metal ions are widely recognized as a key factor for the conformational changes and aggregation of the Alzheimer's disease amyloid (Aβ). So far Al3+ has received much less attention than other biometals in terms of interaction with Aβ. Brain endothelial cells have been identified as important regulators of the neuronal microenvironment, including Aβ levels. The purpose of this study is to compare the effects of the complex amyloid (Aβ1-42)-Al, from human and rat, with the effects produced by metal-free Aβ on rat neuroendothelial cells (NECs). To establish Aβ and Aβ-Al toxicity on NECs, survival, vitality, and angiogenesis are evaluated. Cell survival is reduced by human and rat Aβ in a time-dependent manner. This toxic effect is remarkably pronounced in the presence of human Aβ-Al. Moreover, rat Aβ has anti-angiogenic properties on NECs, and this effect is aggravated dramatically by using both human and rat Aβ-Al complexes. The data and arguments presented herein clearly demonstrate the involvement of Al3+ in Aβ aggregation and, consequently, increasing endothelial cell toxicity.
Keywords: Alzheimer, amyloid, aluminum, metal ions, blood-brain barrier, endothelial cells
