{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:03:28Z","timestamp":1785542608218,"version":"3.56.0"},"reference-count":61,"publisher":"Society for Neuroscience","issue":"4","license":[{"start":{"date-parts":[[2007,7,24]],"date-time":"2007-07-24T00:00:00Z","timestamp":1185235200000},"content-version":"vor","delay-in-days":181,"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":[[2007,1,24]]},"abstract":"<jats:p>The reason why vulnerabilities to mutant polyglutamine (polyQ) proteins are different among neuronal subtypes is mostly unknown. In this study, we compared the gene expression profiles of three types of primary neurons expressing huntingtin (htt) or ataxin-1. We found that heat shock protein 70 (<jats:italic>hsp70<\/jats:italic>), a well known chaperone molecule protecting neurons in the polyQ pathology, was dramatically upregulated only by mutant htt and selectively in the granule cells of the cerebellum. Granule cells, which are insensitive to degeneration in the human Huntington's disease (HD) pathology, lost their resistance by suppressing<jats:italic>hsp70<\/jats:italic>with siRNA, whereas cortical neurons, affected in human HD, gained resistance by overexpressing<jats:italic>hsp70<\/jats:italic>. This indicates that induction levels of<jats:italic>hsp70<\/jats:italic>are a critical factor for determining vulnerabilities to mutant htt among neuronal subtypes. CAT (chloramphenicol acetyltransferase) assays showed that CBF (CCAAT box binding factor, CCAAT\/enhancer binding protein \u03b6) activated, but p53 repressed transcription of the<jats:italic>hsp70<\/jats:italic>gene in granule cells. Basal and mutant htt-induced expression levels of p53 were remarkably lower in granule cells than in cortical neurons, suggesting that different magnitudes of p53 are linked to distinct induction levels of<jats:italic>hsp70<\/jats:italic>. Surprisingly, however, heat shock factor 1 was not activated in granule cells by mutant htt. Collectively, different levels of<jats:italic>hsp70<\/jats:italic>among neuronal subtypes might be involved in selective neuronal death in the HD pathology.<\/jats:p>","DOI":"10.1523\/jneurosci.4522-06.2007","type":"journal-article","created":{"date-parts":[[2007,1,25]],"date-time":"2007-01-25T04:28:57Z","timestamp":1169699337000},"page":"868-880","source":"Crossref","is-referenced-by-count":73,"title":["The Induction Levels of Heat Shock Protein 70 Differentiate the Vulnerabilities to Mutant Huntingtin among Neuronal 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