Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration

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外文摘要：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 supple-menting 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.

外文关键词：

gut dysbiosisintestinal renewalneuron disease

作者：

Yinghui Li、Xingchen Liu、Xue Sun、Hui Li、Shige Wang、Wotu Tian、Chen Xiang、Xuyuan Zhang、Jiajia Zheng、Haifang Wang、Liguo Zhang、Li Cao、Catherine C.L.Wong、Zhihua Liu

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作者单位：

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

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出版年：

2024

DOI：

10.1093/procel/pwae016

蛋白质与细胞

CSTPCD

影响因子：0.645

ISSN：

年,卷(期)：2024.15(11)