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Tauroursodeoxycholic acid prevents E22Q Alzheimer's A beta toxicity in human cerebral endothelial cells

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dc.contributor.authorViana, R. J. S.
dc.contributor.authorNunes, A. F.
dc.contributor.authorCastro, R. E.
dc.contributor.authorRamalho, R. M.
dc.contributor.authorMeyerson, J.
dc.contributor.authorFossati, S.
dc.contributor.authorGhiso, J.
dc.contributor.authorRostagno, A.
dc.contributor.authorRodrigues, C. M. P.
dc.date.accessioned2015-12-30T10:17:30Z
dc.date.available2015-12-30T10:17:30Z
dc.date.issued2009
dc.description.abstractThe vasculotropic E22Q mutant of the amyloid-beta (A beta) peptide is associated with hereditary cerebral hemorrhage with amyloidosis Dutch type. The cellular mechanism(s) of toxicity and nature of the A beta E22Q toxic assemblies are not completely understood. Comparative assessment of structural parameters and cell death mechanisms elicited in primary human cerebral endothelial cells by A beta E22Q and wild-type A beta revealed that only A beta E22Q triggered the Bax mitochondrial pathway of apoptosis. A beta E22Q neither matched the fast oligomerization kinetics of A beta 42 nor reached its predominant beta-sheet structure, achieving a modest degree of oligomerization with a secondary structure that remained a mixture of beta and random conformations. The endogenous molecule tauroursodeoxycholic acid (TUDCA) was a strong modulator of A beta E22Q-triggered apoptosis but did not significantly change the secondary structures and fibrillogenic propensities of A beta peptides. These data dissociate the pro-apoptotic properties of A beta peptides from their distinct mechanisms of aggregation/fibrillization in vitro, providing new perspectives for modulation of amyloid toxicity.. - Fundacao para a Ciencia e a Tecnologia (FCT), Lisbon, Portugal [PTDC/BIABCM/67922/2006, BD/30467/2006, BPD/34603/2007, BPD/30257/2006, BPD/40623/2007]; NIH [NS051715, AG10491]; American Heart Association.. - This work was supported by grant PTDC/BIABCM/67922/2006 from Fundacao para a Ciencia e a Tecnologia (FCT), Lisbon, Portugal; NIH grants NS051715 andAG10491; and the American Heart Association. R.J.S.V. is the recipient of a PhD fellowship from FCT, Portugal (BD/30467/2006); A.F.N., R.E.C. and R. M. R. are recipients of postdoctoral fellowships from FCT, Portugal (BPD/34603/2007, BPD/30257/2006 and BPD/40623/2007, respectively).
dc.formatapplication/pdf
dc.identifier.citationCELLULAR AND MOLECULAR LIFE SCIENCES. - Vol. 66, n. 6 (MAR 2009), p. 1094-1104
dc.identifier.doihttp://dx.doi.org/10.1007/s00018-009-8746-x
dc.identifier.issn1420-682X
dc.identifier.urihttp://hdl.handle.net/10451/21100
dc.language.isoeng
dc.publisherBIRKHAUSER VERLAG AG
dc.subjectBiochemistry & Molecular Biology
dc.subjectCell Biology
dc.titleTauroursodeoxycholic acid prevents E22Q Alzheimer's A beta toxicity in human cerebral endothelial cells
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1104por
oaire.citation.startPage1094por
oaire.citation.titleCELLULAR AND MOLECULAR LIFE SCIENCESpor
oaire.citation.volumeVol. 66por
rcaap.rightsrestrictedAccess
rcaap.typearticle

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