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 dis...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.展开更多
Currently,coronavirus disease 2019(COVID-19)is still spreading in a global scale,exerting a massive health and socioeconomic crisis.Deep insights into the molecular functions of the viral proteins and the pathogenesis...Currently,coronavirus disease 2019(COVID-19)is still spreading in a global scale,exerting a massive health and socioeconomic crisis.Deep insights into the molecular functions of the viral proteins and the pathogenesis of this infectious disease are urgently needed.In this review,we comprehensively describe the proteome of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and summarize their protein interaction map with host cells.In the protein interaction network between the virus and the host,a total of 787 host prey proteins that appeared in at least two studies or were verified by co-immunoprecipitation experiments.Together with 29 viral proteins,a network of 1762 proximal interactions were observed.We also review the proteomics results of COVID-19 patients and proved that SARS-CoV-2 hijacked the host’s translation system,post-translation modification system,and energy supply system via viral proteins,resulting in various immune disorders,multiple cardiomyopathies,and cholesterol metabolism diseases.展开更多
基金supported by Tsinghua-Peking Center for Life Sciences,the National Key Research and Development Program of China(2018YFE0207300,2017YFA0503403)the National Natural Science Foundation of China(Grant Nos.31730028,82001681,81870889,82071258)+1 种基金Training Program of the Big Science Strategy Plan(2020YFE0202200)the Research Fund from Vanke School of Public Health of Tsinghua University.
文摘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.
基金This work is supported by Clinical Research Operating Fund of Central High level hospitals,Training Program of the Big Science Strategy Plan 2020YFE0202200National Natural Science Foundation of China Grants 32150005Research Funds from Health@InnoHK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region.
文摘Currently,coronavirus disease 2019(COVID-19)is still spreading in a global scale,exerting a massive health and socioeconomic crisis.Deep insights into the molecular functions of the viral proteins and the pathogenesis of this infectious disease are urgently needed.In this review,we comprehensively describe the proteome of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and summarize their protein interaction map with host cells.In the protein interaction network between the virus and the host,a total of 787 host prey proteins that appeared in at least two studies or were verified by co-immunoprecipitation experiments.Together with 29 viral proteins,a network of 1762 proximal interactions were observed.We also review the proteomics results of COVID-19 patients and proved that SARS-CoV-2 hijacked the host’s translation system,post-translation modification system,and energy supply system via viral proteins,resulting in various immune disorders,multiple cardiomyopathies,and cholesterol metabolism diseases.
