{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:17:57Z","timestamp":1791256677511,"version":"4.1.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,2,12]]},"abstract":"<jats:p>\n                    Administration of \u03b2-sitosterol (42 mg\/kg per day) for 3 weeks to 8-month-old male LXR\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice resulted in the death of motor neurons in the lumbar region of the spinal cord and loss of tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra. In mice at 5 months of age, \u03b2-sitosterol had no observed toxicity but at 16 months of age, it caused severe paralysis and symptoms typical of dopaminergic dysfunction in LXR\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. WT mice were not affected by these doses of \u03b2-sitosterol. In 5-month-old mice, levels of the intestinal transporters, ABCG5\/8 and Niemann-Pick C1 Like 1, were not affected by loss of liver X receptor (LXR) \u03b2 and\/or treatment with \u03b2-sitosterol nor were there changes in plasma levels of cholesterol or \u03b2-sitosterol. In 8-month-old LXR\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice there was activation of microglia in the substantia nigra pars reticulata and aggregates of ubiquitin and TDP-43 in the cytoplasm of large motor neurons in the lumbar spinal cord. Brain cholesterol concentrations were higher in LXR\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    than in their WT counterparts, and treatment with \u03b2-sitosterol reduced brain cholesterol in both WT and LXR\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In LXR\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice but not in WT mice levels of 24-hydrocholesterol were increased upon \u03b2-sitosterol treatment. These data indicate that multiple mechanisms are involved in the sensitivity of LXR\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice to \u03b2-sitosterol. These include activation of microglia, accumulation of protein aggregates in the cytoplasm of large motor neurons, and depletion of brain cholesterol.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0711599105","type":"journal-article","created":{"date-parts":[[2008,1,31]],"date-time":"2008-01-31T20:54:10Z","timestamp":1201812850000},"page":"2094-2099","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":128,"title":["Liver X receptor \u03b2 (LXR\u03b2): A link between \u03b2-sitosterol and amyotrophic lateral sclerosis\u2013Parkinson's dementia"],"prefix":"10.1073","volume":"105","author":[{"given":"Hyun-Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Departments of *Biosciences and Nutrition and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotang","family":"Fan","sequence":"additional","affiliation":[{"name":"Departments of *Biosciences and Nutrition 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