Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation

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• dc.contributor.author Guix Ràfols, Francesc Xavier
• dc.contributor.author Ill-Raga, Gerard, 1982-
• dc.contributor.author Bravo, Ramona
• dc.contributor.author Nakaya, Tadashi
• dc.contributor.author De Fabritiis, Gianni
• dc.contributor.author Coma Camprodón, Mireia
• dc.contributor.author Miscione, Gian Pietro
• dc.contributor.author Villà i Freixa, Jordi
• dc.contributor.author Suzuki, Toshiharu
• dc.contributor.author Fernàndez Busquets, Xavier
• dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-
• dc.contributor.author De Strooper, Bart
• dc.contributor.author Muñoz López, Francisco José, 1964-
• dc.date.accessioned 2024-06-20T14:57:29Z
• dc.date.available 2024-06-20T14:57:29Z
• dc.date.issued 2009
• dc.description.abstract Alzheimer's disease neuropathology is characterized by neuronal death, amyloid beta-peptide deposits and neurofibrillary tangles composed of paired helical filaments of tau protein. Although crucial for our understanding of the pathogenesis of Alzheimer's disease, the molecular mechanisms linking amyloid beta-peptide and paired helical filaments remain unknown. Here, we show that amyloid beta-peptide-induced nitro-oxidative damage promotes the nitrotyrosination of the glycolytic enzyme triosephosphate isomerase in human neuroblastoma cells. Consequently, nitro-triosephosphate isomerase was found to be present in brain slides from double transgenic mice overexpressing human amyloid precursor protein and presenilin 1, and in Alzheimer's disease patients. Higher levels of nitro-triosephosphate isomerase (P < 0.05) were detected, by Western blot, in immunoprecipitates from hippocampus (9 individuals) and frontal cortex (13 individuals) of Alzheimer's disease patients, compared with healthy subjects (4 and 9 individuals, respectively). Triosephosphate isomerase nitrotyrosination decreases the glycolytic flow. Moreover, during its isomerase activity, it triggers the production of the highly neurotoxic methylglyoxal (n = 4; P < 0.05). The bioinformatics simulation of the nitration of tyrosines 164 and 208, close to the catalytic centre, fits with a reduced isomerase activity. Human embryonic kidney (HEK) cells overexpressing double mutant triosephosphate isomerase (Tyr164 and 208 by Phe164 and 208) showed high methylglyoxal production. This finding correlates with the widespread glycation immunostaining in Alzheimer's disease cortex and hippocampus from double transgenic mice overexpressing amyloid precursor protein and presenilin 1. Furthermore, nitro-triosephosphate isomerase formed large beta-sheet aggregates in vitro and in vivo, as demonstrated by turbidometric analysis and electron microscopy. Transmission electron microscopy (TEM) and atomic force microscopy studies have demonstrated that nitro-triosephosphate isomerase binds tau monomers and induces tau aggregation to form paired helical filaments, the characteristic intracellular hallmark of Alzheimer's disease brains. Our results link oxidative stress, the main etiopathogenic mechanism in sporadic Alzheimer's disease, via the production of peroxynitrite and nitrotyrosination of triosephosphate isomerase, to amyloid beta-peptide-induced toxicity and tau pathology.
• dc.description.sponsorship Spanish Ministerio de Sanidad (FIS: PRO1208; Red HERACLES RD06/0009/002); Educación y Ciencia (BIO2005-01591, SAF2006-4973, CSD2006-00012); Generalitat de Catalunya (GSR2005-266; 2005-SGR00037); EC funded STREP project QosCosGrid (IST-033883); VPH NOE (ICT-223920); Methusalem grant of the Flemish government (to lab of BDS); VIB and KUL (to lab of BDS).
• dc.format.mimetype application/pdf
• dc.identifier.citation Guix FX, Ill-Raga G, Bravo R, Nakaya T, de Fabritiis G, Coma M, et al. Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation. Brain. 2009 May;132(Pt 5):1335-45. DOI: 10.1093/brain/awp023
• dc.identifier.doi http://dx.doi.org/10.1093/brain/awp023
• dc.identifier.issn 0006-8950
• dc.identifier.uri http://hdl.handle.net/10230/60551
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Brain. 2009 May;132(Pt 5):1335-45
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BIO2005-01591
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2006-4973
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/CSD2006-00012
• dc.rights © Oxford University Press. This is a pre-copyedited, author-produced version of an article accepted for publication in Brain: a journal of neurology following peer review. The version of record Guix FX, Ill-Raga G, Bravo R, Nakaya T, de Fabritiis G, Coma M, et al. Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation. Brain. 2009 May;132(Pt 5):1335-45. DOI: 10.1093/brain/awp023 is available online at: http://dx.doi.org/10.1093/brain/awp023
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Alzheimer’s disease
• dc.subject.keyword Amyloid ß-peptide
• dc.subject.keyword Tau protein
• dc.subject.keyword Triosephosphate isomerase
• dc.subject.keyword Peroxynitrite
• dc.title Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion