{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T13:34:41Z","timestamp":1771853681268,"version":"3.50.1"},"reference-count":43,"publisher":"Proceedings of the National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,8,15]]},"abstract":"<jats:p>Huntington's disease (HD) is an autosomal dominant neurodegenerative condition caused by expansions of more than 35 uninterrupted CAG repeats in exon 1 of the huntingtin gene. The CAG repeats in HD and the other seven known diseases caused by CAG codon expansions are translated into long polyglutamine tracts that confer a deleterious gain of function on the mutant proteins. Intraneuronal inclusions comprising aggregates of the relevant mutant proteins are found in the brains of patients with HD and related diseases. It is crucial to determine whether the formation of inclusions is directly pathogenic, because a number of studies have suggested that aggregates may be epiphenomena or even protective. Here, we show that fragments of the bacterial chaperone GroEL and the full-length yeast heat shock protein Hsp104 reduce both aggregate formation and cell death in mammalian cell models of HD, consistent with a causal link between aggregation and pathology.<\/jats:p>","DOI":"10.1073\/pnas.170280697","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:41:48Z","timestamp":1027694508000},"page":"9701-9705","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":161,"title":["Bacterial and yeast chaperones reduce both aggregate formation and cell death in mammalian cell models of Huntington's disease"],"prefix":"10.1073","volume":"97","author":[{"given":"Jenny","family":"Carmichael","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome\/Medical Research Council Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom; Centre for Protein Engineering and Cambridge University Chemical Laboratory, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Chatellier","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome\/Medical Research Council Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom; Centre for Protein Engineering and Cambridge University Chemical Laboratory, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Woolfson","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome\/Medical Research Council Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom; Centre for Protein Engineering and Cambridge University Chemical Laboratory, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9sar","family":"Milstein","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome\/Medical Research Council Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom; Centre for Protein Engineering and Cambridge University Chemical Laboratory, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan R.","family":"Fersht","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome\/Medical Research Council Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom; Centre for Protein Engineering and Cambridge University Chemical Laboratory, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Rubinsztein","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome\/Medical Research Council Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom; Centre for Protein Engineering and Cambridge University Chemical Laboratory, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH,..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2000,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_3_3_2_2","first-page":"265","volume":"36","author":"Rubinsztein D C","year":"1999","unstructured":"D C Rubinsztein, A Wyttenbach, J Rankin J Med Genet 36, 265\u2013270 (1999).","journal-title":"J Med Genet"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.36.10.739"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1990"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440216"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-111"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/40153"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00656-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80943-5"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.7.1185"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.5.913"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1998.0168"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-150"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.5.783"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.6.2898"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.6.997"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0720185.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81782-1"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(98)01350-4"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81781-X"},{"key":"e_1_3_3_23_2","unstructured":"Orr H. 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