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The role of nucleotide-binding domain, leucine-rich\u2013containing family, pyrin domain\u2013containing-3 (NLRP3) inflammasome in HD pathogenesis remains largely uncharacterized. Parthenolide (PTL), a naturally occurring nuclear factor kappa B (NF-\u03baB) inhibitor, is also known to inhibit NLRP3 inflammasome. Whether PTL is beneficial in HD has not been established yet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study evaluated the possible neuroprotective effects of PTL against 3NP-induced behavioural abnormalities, striatal biochemical derangements, and histological aberrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar rats received PTL (0.5\u00a0mg\/kg\/day, i.p) for 3 weeks and 3NP (10\u00a0mg\/kg\/day, i.p) was administered alongside for the latter 2 weeks to induce HD. Finally, animals were subjected to open-field, Morris water maze and rotarod tests. Rat striata were examined histologically, striatal protein expression levels of glial fibrillary acidic protein (GFAP), cluster of differentiation 45 (CD45) and neuron-specific enolase (NSE) were evaluated immunohistochemically, while those of interleukin (IL)-1\u03b2, IL-18, ionized calcium-binding adapter molecule-1 (Iba1) and glutamate were determined by ELISA. Striatal nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein (Keap1), NF-\u03baB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, S100 calcium-binding protein A10 (S100A10) and complement-3 (C3) were assessed by gene expression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PTL improved motor, locomotor, cognitive and anxiety-like behaviours, restored neuronal integrity, upregulated Nrf2, and inhibited NLRP3 inflammasome, NF-\u03baB and microglial activation. Additionally, PTL induced astrocyte shifting towards the neuroprotective A2 phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PTL exhibits neuroprotection against 3NP-induced HD, that might be ascribed, at least in part, to its modulatory effects on Keap1\/Nrf2 and NF-\u03baB\/NLRP3 inflammasome signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-024-00917-5","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T06:03:05Z","timestamp":1727330585000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Parthenolide ameliorates 3-nitropropionic acid-induced Huntington\u2019s disease-like aberrations via modulating NLRP3 inflammasome, reducing microglial activation and inducing astrocyte shifting"],"prefix":"10.1186","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6679-7862","authenticated-orcid":false,"given":"Mona E.","family":"Noureldeen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9746-5335","authenticated-orcid":false,"given":"Nancy N.","family":"Shahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3311-4840","authenticated-orcid":false,"given":"Hebat Allah A.","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-4392","authenticated-orcid":false,"given":"Maha M.","family":"El-Sawalhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4765-0353","authenticated-orcid":false,"given":"Heba R.","family":"Ghaiad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"917_CR1","doi-asserted-by":"crossref","unstructured":"Abdel Rasheed NO, Ibrahim WW. 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