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dc.contributor.authorRoodveldt, Cintia-
dc.contributor.authorFernández Montesinos, Rafael-
dc.contributor.authorPozo, David-
dc.contributor.authorDobson, Christopher M.-
dc.identifier.citationEMBO Journal 28(23): 3758-3770 (2009)es_ES
dc.description13 páginas, 6 figuras.-- et al.es_ES
dc.description.abstractThe ATP-dependent protein chaperone heat-shock protein 70 (Hsp70) displays broad anti-aggregation functions and has a critical function in preventing protein misfolding pathologies. According to in vitro and in vivo models of Parkinson's disease (PD), loss of Hsp70 activity is associated with neurodegeneration and the formation of amyloid deposits of α-synuclein (αSyn), which constitute the intraneuronal inclusions in PD patients known as Lewy bodies. Here, we show that Hsp70 depletion can be a direct result of the presence of aggregation-prone polypeptides. We show a nucleotide-dependent interaction between Hsp70 and αSyn, which leads to the aggregation of Hsp70, in the presence of ADP along with αSyn. Such a co-aggregation phenomenon can be prevented in vitro by the co-chaperone Hip (ST13), and the hypothesis that it might do so also in vivo is supported by studies of a Caenorhabditis elegans model of αSyn aggregation. Our findings indicate that a decreased expression of Hip could facilitate depletion of Hsp70 by amyloidogenic polypeptides, impairing chaperone proteostasis and stimulating neurodegeneration.es_ES
dc.description.sponsorshipCR and AA held FEBS Long-Term Fellowships. CWB is an EMBO Long-Term Postdoctoral Fellow, ATvdG was the recipient of a Topmaster fellowship of the graduate school GUIDE for Drug Exploration of the University of Groningen. STDH is a recipient of a Human Frontier Science Program Long-termFellowship (LT0798/ 2005) and is supported in part by the National Science Council of the Republic of China, Taiwan(NSC97-2917-1-564-102). JC is recipient of a Human Frontier Young Investigators Award (RGY67/ 2007) and also thanks the BBSRC (9015651/1). CMD and JC acknowledge funding from The Wellcome Trust and The Leverhulme Trust. DP is grateful to The Spanish Ministry of Health (PI05/2056; PI06/1641), The Spanish Ministry of Science and Innovation (SAF2007-29418E) and the PAIDI Program from the Regional Government (BIO323) for funding. EAAN acknowledges ZonMW Research Institute of Diseases in the Elderly and De Nederlandse Hersenstichting for funding.es_ES
dc.publisherNature Publishing Groupes_ES
dc.publisherEuropean Molecular Biology Organizationes_ES
dc.subjectParkinson's diseasees_ES
dc.titleChaperone proteostasis in Parkinson's disease: stabilization of the Hsp70/α-synuclein complex by Hipes_ES
dc.description.peerreviewedPeer reviewedes_ES
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