{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T08:21:07Z","timestamp":1774599667060,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T00:00:00Z","timestamp":1452470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["50\u201014\u201000068"],"award-info":[{"award-number":["50\u201014\u201000068"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The common feature of Huntington disease is the accumulation of oligomers or aggregates of mutant huntingtin protein (m<jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content>), which causes the death of a subset of striatal neuronal populations. The cytotoxic species can leave neurons and migrate to other groups of cells penetrating and damaging them in a prion\u2010like manner. We hypothesized that the glycolytic enzyme glyceraldehyde 3\u2010phosphate dehydrogenase (<jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content>), previously shown to elevate the aggregation of m<jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content>, is associated with an increased efficiency of intercellular propagation of m<jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content>, on its own or together with polyglutamine species, was shown to be released into the extracellular milieu mainly from dying cells as assessed by a novel enzyme immunoassay, western blotting, and ultrafiltration. The conditioned medium of cells with growing <jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content>\u2010polyQ aggregates was toxic to na\u00efve cells, whereas depletion of the aggregates from the medium lowered this cytotoxicity. The <jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content> component of the aggregates was found to increase their toxicity by two\u2010fold in comparison with polyQ alone. Furthermore, <jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content>\u2010polyQ complexes were shown to penetrate acceptor cells and to increase the capacity of polyQ to prionize its intracellular homolog containing a repeat of 25 glutamine residues. Finally, inhibitors of intracellular transport showed that polyQ\u2010<jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content> complexes, as well as <jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content> itself, penetrated cells using clathrin\u2010mediated endocytosis. This suggested a pivotal role of the enzyme in the intercellular transmission of Huntington disease pathogenicity. In conclusion, <jats:styled-content style=\"fixed-case\">GAPDH<\/jats:styled-content> occurring in complexes with polyglutamine strengthens the prion\u2010like activity and toxicity of the migrating aggregates.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13463-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>Aggregating polygluatmine tracts were shown to release from the cells over\u2010expressing mutant huntingtin in a complex with glyceraldehyde 3\u2010phosphate dehydrogenase (GAPDH). The enzyme enhances the intracellular transport of aggregates to healthy cells, prionization of normal cellular proteins and finally cell death, thus demonstrating the pivotal role of GAPDH in the horizontal transmission of neurodegeneration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13463","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T15:24:57Z","timestamp":1449761097000},"page":"1052-1063","source":"Crossref","is-referenced-by-count":17,"title":["Glyceraldehyde 3\u2010phosphate dehydrogenase augments the intercellular transmission and toxicity of polyglutamine aggregates in a cell model of Huntington disease"],"prefix":"10.1111","volume":"136","author":[{"given":"Elena R.","family":"Mikhaylova","sequence":"first","affiliation":[{"name":"Laboratory of Cell Protection Mechanisms Institute of Cytology of the Russian Academy of Sciences St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir F.","family":"Lazarev","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Protection Mechanisms Institute of Cytology of the Russian Academy of Sciences St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina D.","family":"Nikotina","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Protection Mechanisms Institute of Cytology of the Russian Academy of Sciences St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris A.","family":"Margulis","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Protection Mechanisms Institute of Cytology of the Russian Academy of Sciences St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina V.","family":"Guzhova","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Protection Mechanisms Institute of Cytology of the Russian Academy of Sciences St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi443"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511316103"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2873"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr477"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.patbio.2014.08.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05537.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr314"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835a3ee0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.346072"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-014-0554-z"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-38"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.9.1311"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.32607\/20758251-2013-5-2-81-89","article-title":"Factors affecting aggregate formation in cell models of Huntington's disease and amyotrophic lateral sclerosis","volume":"5","author":"Lazarev V. 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