{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:39:36Z","timestamp":1791956376409,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2014\u201053763\u2010P"],"award-info":[{"award-number":["SAF2014\u201053763\u2010P"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RTC\u20102015\u20103364"],"award-info":[{"award-number":["RTC\u20102015\u20103364"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Phytocannabinoids are produced in\n \n Cannabis sativa<\/jats:italic>\n <\/jats:styled-content>\n L. in acidic form and are decarboxylated upon heating, processing and storage. While the biological effects of decarboxylated cannabinoids such as \u0394\n 9<\/jats:sup>\n \u2010tetrahydrocannabinol have been extensively investigated, the bioactivity of \u0394\n 9<\/jats:sup>\n \u2010tetahydrocannabinol acid (\u0394\n 9<\/jats:sup>\n \u2010THCA) is largely unknown, despite its occurrence in different\n Cannabis<\/jats:italic>\n preparations. Here we have assessed possible neuroprotective actions of \u0394\n 9<\/jats:sup>\n \u2010THCA through modulation of PPAR\u03b3 pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n The effects of six phytocannabinoids on PPAR\u03b3 binding and transcriptional activity were investigated. The effect of \u0394\n 9<\/jats:sup>\n \u2010THCA on mitochondrial biogenesis and PPAR\u03b3 coactivator 1\u2010\u03b1 expression was investigated in Neuro\u20102a (N2a) cells. The neuroprotective effect was analysed in ST\n Hdh<\/jats:italic>\n Q111\/Q111<\/jats:sup>\n cells expressing a mutated form of the huntingtin protein and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt\u2010q94). The\n in vivo<\/jats:italic>\n neuroprotective activity of \u0394\n 9<\/jats:sup>\n \u2010THCA was investigated in mice intoxicated with the mitochondrial toxin 3\u2010nitropropionic acid (3\u2010NPA).\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Cannabinoid acids bind and activate PPAR\u03b3 with higher potency than their decarboxylated products. \u0394\n 9<\/jats:sup>\n \u2010THCA increased mitochondrial mass in neuroblastoma N2a cells and prevented cytotoxicity induced by serum deprivation in ST\n Hdh<\/jats:italic>\n Q111\/Q111<\/jats:sup>\n cells and by mutHtt\u2010q94 in N2a cells. \u0394\n 9<\/jats:sup>\n \u2010THCA, through a PPAR\u03b3\u2010dependent pathway, was neuroprotective in mice treated with 3\u2010NPA, improving motor deficits and preventing striatal degeneration. In addition, \u0394\n 9<\/jats:sup>\n \u2010THCA attenuated microgliosis, astrogliosis and up\u2010regulation of proinflammatory markers induced by 3\u2010NPA.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n \u0394\n 9<\/jats:sup>\n \u2010THCA shows potent neuroprotective activity, which is worth considering for the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.14019","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T23:06:41Z","timestamp":1504048001000},"page":"4263-4276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["Tetrahydrocannabinolic acid is a potent PPAR\u03b3 agonist with neuroprotective activity"],"prefix":"10.1111","volume":"174","author":[{"given":"Xavier","family":"Nadal","sequence":"first","affiliation":[{"name":"Phytoplant 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