{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:05:11Z","timestamp":1793333111269,"version":"4.5.0"},"reference-count":44,"publisher":"Society for Neuroscience","issue":"30","license":[{"start":{"date-parts":[[2008,1,25]],"date-time":"2008-01-25T00:00:00Z","timestamp":1201219200000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,7,25]]},"abstract":"<jats:p>\n                    The heat shock transcription factors (Hsfs) are responsible for the heat shock response, an evolutionarily conserved process for clearance of damaged and aggregated proteins. In organisms such as\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , which contain a single Hsf, reduction in the level of Hsf is associated with the appearance of age-related phenotypes and increased accumulation of protein aggregates. Mammalian cells express three\n                    <jats:italic>hsfs<\/jats:italic>\n                    (\n                    <jats:italic>hsf1<\/jats:italic>\n                    ,\n                    <jats:italic>hsf2<\/jats:italic>\n                    ,\n                    <jats:italic>hsf4<\/jats:italic>\n                    ) and their role in CNS homeostasis remains unclear. In this study, we examined the effects of deletion of single or multiple\n                    <jats:italic>hsf<\/jats:italic>\n                    genes in the CNS using mutant mice. Our results show that\n                    <jats:italic>hsf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice display progressive myelin loss that accompanies severe astrogliosis and this is exacerbated in the absence of either the\n                    <jats:italic>hsf2<\/jats:italic>\n                    or\n                    <jats:italic>hsf4<\/jats:italic>\n                    gene. Magnetic resonance imaging and behavioral studies indicate reduction in the white matter tracts of the corpus callosum, and deficiencies in motor activity, respectively, in aged\n                    <jats:italic>hsf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Concomitantly,\n                    <jats:italic>hsf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    aged CNS exhibit increased activated microglia and apoptotic cells that are mainly positive for GFAP, an astrocyte-specific marker. Studies based on the expression of short-lived ubiquitinated green fluorescent protein (GFPu) in living\n                    <jats:italic>hsf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    cells indicate that they exhibit reduced ability to degrade ubiquitinated proteins, accumulate short-lived GFPu, and accumulate aggregates of the Huntington's model of GFP containing trinucleotide repeats (Q103-GFP). Likewise,\n                    <jats:italic>hsf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    brain and astrocytes exhibit higher than wild-type levels of ubiquitinated proteins, increased levels of protein oxidation, and increased sensitivity to oxidative stress. These studies indicate a critical role for mammalian\n                    <jats:italic>hsf<\/jats:italic>\n                    genes, but specifically\n                    <jats:italic>hsf1<\/jats:italic>\n                    , in the quality control mechanisms and maintenance of CNS homeostasis during the organism's lifetime.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0006-07.2007","type":"journal-article","created":{"date-parts":[[2007,7,25]],"date-time":"2007-07-25T13:39:30Z","timestamp":1185370770000},"page":"7974-7986","source":"Crossref","is-referenced-by-count":86,"title":["Demyelination, Astrogliosis, and Accumulation of Ubiquitinated Proteins, Hallmarks of CNS Disease in\n                    <i>hsf1<\/i>\n                    -Deficient Mice"],"prefix":"10.1523","volume":"27","author":[{"given":"Sachiko","family":"Homma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongjie","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naxin","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinna","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Yanasak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahid 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