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Here, we identified therapeutic potential of perillaldehyde (PAE), a monoterpene compound obtained from\n                    <jats:italic>Perilla frutescens<\/jats:italic>\n                    (L.) Britt., in the\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    (\n                    <jats:italic>C. elegans<\/jats:italic>\n                    ) model of HD, which included lifespan extension, healthspan improvement, decrease in polyglutamine (polyQ) aggregation, and preservation of mitochondrial network. Further analyses indicated that PAE was able to induce autophagy and mitochondrial unfolded protein reaction (UPR\n                    <jats:sup>mt<\/jats:sup>\n                    ) activation and positively regulated expression of associated genes. In\n                    <jats:italic>lgg\u20101<\/jats:italic>\n                    RNAi\n                    <jats:italic>C. elegans<\/jats:italic>\n                    or\n                    <jats:italic>C. elegans<\/jats:italic>\n                    with UPR\n                    <jats:sup>mt<\/jats:sup>\n                    \u2010related genes knockdown, the effects of PAE treatment on polyQ aggregation or rescue polyQ\u2010induced toxicity were attenuated, suggesting that its neuroprotective activity depended on autophagy and UPR\n                    <jats:sup>mt<\/jats:sup>\n                    . Moreover, we found that pharmacological and genetic activation of UPR\n                    <jats:sup>mt<\/jats:sup>\n                    generally protected\n                    <jats:italic>C. elegans<\/jats:italic>\n                    from polyQ\u2010induced cytotoxicity. Finally, PAE promoted serotonin synthesis by upregulating expression of TPH\u20101, and serotonin synthesis and neurosecretion were required for PAE\u2010mediated UPR\n                    <jats:sup>mt<\/jats:sup>\n                    activation and its neuroprotective activity. In conclusion, PAE is a potential therapy for polyQ\u2010related diseases including HD, which is dependent on autophagy and cell\u2010non\u2010autonomous UPR\n                    <jats:sup>mt<\/jats:sup>\n                    activation.\n                  <\/jats:p>","DOI":"10.1002\/biof.2089","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T09:20:19Z","timestamp":1720689619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Perillaldehyde alleviates\n                    <scp>polyQ<\/scp>\n                    \u2010induced neurodegeneration through the induction of autophagy and mitochondrial\n                    <scp>UPR<\/scp>\n                    in\n                    <scp>\n                      <i>Caenorhabditis elegans<\/i>\n                    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