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Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.<\/jats:p>","DOI":"10.1093\/procel\/pwae016","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T19:19:24Z","timestamp":1713467964000},"page":"818-839","source":"Crossref","is-referenced-by-count":10,"title":["Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration"],"prefix":"10.1093","volume":"15","author":[{"given":"Yinghui","family":"Li","sequence":"first","affiliation":[{"name":"Institute for Immunology and School of Basic Medicine, Tsinghua University , Beijing 100084 ,","place":["China"]},{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"Institute of 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