. Institute for Immunology and School of Basic Medicine, Tsinghua University, Beijing 100084, China . Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China . Institute of Biophysics, University of Chinese Academy of Sciences, Beijing 100049, China . Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China . First School of Clinical Medicine, Peking University First Hospital, Peking University, Beijing 100034, China . School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, United States . Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China . Department of Laboratory Medicine, Peking University Third Hospital, Beijing, 100191, China . Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China . Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China . Tsinghua University-Peking University Joint Center for Life Sciences, Peking University, Beijing 100084, China
Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson’s disease. 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.
Corresponding Author(s):
Li Cao,Catherine C.L. Wong,Zhihua Liu
Online First Date: 29 July 2024Issue Date: 29 November 2024
Cite this article:
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