Intracellular amyloid formation in muscle cells of Abeta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification.

Mol. Neurodegener.

dc.creatorMinniti, AN
dc.creatorRebolledo, DL
dc.creatorGrez, PM
dc.creatorFadic, R
dc.creatorAldunate, R
dc.creatorVolitakis, I
dc.creatorCherny, R.A.
dc.creatorOpazo, C.
dc.creatorMasters, C.
dc.creatorBush, A.I.
dc.creatorInestrosa, N.C.
dc.date2019-12-18T18:14:59Z
dc.date2022-07-07T23:39:27Z
dc.date2019-12-18T18:14:59Z
dc.date2022-07-07T23:39:27Z
dc.date2009
dc.date.accessioned2023-08-22T02:04:18Z
dc.date.available2023-08-22T02:04:18Z
dc.identifier13980001
dc.identifier13980001
dc.identifierhttps://hdl.handle.net/10533/237204
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8308957
dc.descriptionBACKGROUND: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Abeta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Abeta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Abeta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. RESULTS: In the present work, we found that intracellular Abeta aggregation in muscle cells of Caenorhabditis elegans overexpressing Abeta peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Abeta. We show that intracellular amyloid aggregation of wild type Abeta is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Abeta-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. CONCLUSION: Our data show that intracellular Abeta amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Abeta aggregation may be part of a cell protective mechanism.
dc.descriptionFONDAP
dc.descriptionFONDAP
dc.languageeng
dc.relationinstname: Conicyt
dc.relationreponame: Repositorio Digital RI2.0
dc.relationinfo:eu-repo/grantAgreement/Fondap/13980001
dc.relationhttps://www.ncbi.nlm.nih.gov/pubmed/19126228
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleIntracellular amyloid formation in muscle cells of Abeta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification.
dc.titleMol. Neurodegener.
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion


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