Neuroprotective properties of copper binding fragments of amyloid precursor protein and prion

Abstract

We are particularly interested in the neurobiology of copper as a start point to understand the role of this metal on neurodevelopmental as well as in neurodegenerative processes. Here, we summarize our evidence that support a role in copper homeostasis of the amyloid precursor protein (APP), a protein related to Alzheimer's disease, and the Prion protein (PrP), which is related to the Creutzfeldt–Jakob disease. First, APP and PrP possess copper reduction activity, measured by the bathocuproine assay, being cysteine and tryptophan key amino acids for oxidation (in APP and PrP, respectively). Second, PrP transcription is regulated by copper, both in primary neuronal cultures and in PC12 cell lines transfected with the PrP promoter. Finally, APP‐ and PrP‐copper binding domains rescue rats from copper induced neurotoxicity and spatial memory deficits induced by metal injection into the rat brain. Since APP and PrP proteins are localized at the plasma membrane, we proposed that their abilities to bind and reduce copper might play an important role as a primary neuronal response against copper neurotoxicity.Acknowledgements: Supported by FONDECYT No. 2990087 to C.O. and CIMM‐ICA, FONDAP‐Biomedicine No. 13980001, MIFAB and a Presidential Chair in Science (1999–2001) from the Chilean Government to N.C.I.