The N-terminal copper-binding domain of the amyloid precursor protein protects against Cu<SUP>2+</SUP> neurotoxicity in vivo

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dc.contributor.authorCerpa, WF
dc.contributor.authorBarría, MI
dc.contributor.authorChacón, MA
dc.contributor.authorSuazo, M
dc.contributor.authorGonzález, M
dc.contributor.authorOpazo, C
dc.contributor.authorBush, AI
dc.contributor.authorInestrosa, NC
dc.date.accessioned2025-01-21T01:07:40Z
dc.date.available2025-01-21T01:07:40Z
dc.date.issued2004
dc.description.abstractThe amyloid precursor protein (APP) contains a Cu binding domain (CuBD) localized between amino acids 135 and 156 (APP(135-156)), which can reduce Cu2+ to Cu1+ in vitro. The physiological function of this APP domain has not yet being established; nevertheless several studies support the notion that the CuBD of APP is involved in Cu homeostasis. We used APP synthetic peptides to evaluate their protective properties against Cu2+ neurotoxicity in a bilateral intra-hippocampal injection model. We found that human APP135-156 protects against Cu2+-induced neurotoxic effects, such as, impairment of spatial memory, neuronal cell loss, and astrogliosis. APP135-156 lacking two histidine residues showed protection against Cu2+; however, APP135-156 mutated in cysteine 144, a key residue in the reduction of Cu2+ to Cu1+, did not protect against Cu2+ neurotoxicity. In accordance with recent reports, the CuBD of the Caenorhabditis elegans, APL-1 protected against Cu2+ neurotoxicity in vivo. We also found that Cu2+ neurotoxicity is associated with an increase in nitrotyrosine immunofluorescence as well as with a decrease in Cu2+ uptake. The CuBD of APP therefore may play a role in the detoxification of brain Cu.
dc.fuente.origenWOS
dc.identifier.doi10.1096/fj.03-1349fje
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttps://doi.org/10.1096/fj.03-1349fje
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96363
dc.identifier.wosidWOS:000224243200045
dc.issue.numero12
dc.language.isoen
dc.pagina.final+
dc.pagina.inicio1701
dc.revistaFaseb journal
dc.rightsacceso restringido
dc.subjectwater maze
dc.subjectintracerebral injection
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe N-terminal copper-binding domain of the amyloid precursor protein protects against Cu<SUP>2+</SUP> neurotoxicity in vivo
dc.typeartículo
dc.volumen18
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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