{"title":"戈谢病为了解帕金森病的发病机制提供了一个独特的窗口。","authors":"Ellen Hertz, Yu Chen, Ellen Sidransky","doi":"10.1038/s41582-024-00999-z","DOIUrl":null,"url":null,"abstract":"An exciting development in the field of neurodegeneration is the association between the rare monogenic disorder Gaucher disease and the common complex disorder Parkinson disease (PD). Gaucher disease is a lysosomal storage disorder resulting from an inherited deficiency of the enzyme glucocerebrosidase, encoded by GBA1, which hydrolyses the glycosphingolipids glucosylceramide and glucosylsphingosine. The observation of parkinsonism in a rare subgroup of individuals with Gaucher disease first directed attention to the role of glucocerebrosidase deficiency in the pathogenesis of PD. PD occurs more frequently in people heterozygous for Gaucher GBA1 mutations, and 3–25% of people with Parkinson disease carry a GBA1 variant. However, only a small percentage of individuals with GBA1 variants develop parkinsonism, suggesting that the penetrance is low. Despite over a decade of intense research in this field, including clinical and radiological evaluations, genetic studies and investigations using model systems, the mechanism underlying GBA1-PD is still being pursued. Insights from this association have emphasized the role of lysosomal pathways in parkinsonism. Furthermore, different therapeutic strategies considered or developed for Gaucher disease can now inform drug development for PD. The association between the rare, monogenic lysosomal storage disorder Gaucher disease and Parkinson disease has provided insights into the pathogenesis of this far more common neurodegenerative disease. Here, Sidransky and colleagues review the knowledge gained from decades of Gaucher disease research and explore the relationship between GBA1 and parkinsonism.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 9","pages":"526-540"},"PeriodicalIF":28.2000,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Gaucher disease provides a unique window into Parkinson disease pathogenesis\",\"authors\":\"Ellen Hertz, Yu Chen, Ellen Sidransky\",\"doi\":\"10.1038/s41582-024-00999-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"An exciting development in the field of neurodegeneration is the association between the rare monogenic disorder Gaucher disease and the common complex disorder Parkinson disease (PD). Gaucher disease is a lysosomal storage disorder resulting from an inherited deficiency of the enzyme glucocerebrosidase, encoded by GBA1, which hydrolyses the glycosphingolipids glucosylceramide and glucosylsphingosine. The observation of parkinsonism in a rare subgroup of individuals with Gaucher disease first directed attention to the role of glucocerebrosidase deficiency in the pathogenesis of PD. PD occurs more frequently in people heterozygous for Gaucher GBA1 mutations, and 3–25% of people with Parkinson disease carry a GBA1 variant. However, only a small percentage of individuals with GBA1 variants develop parkinsonism, suggesting that the penetrance is low. Despite over a decade of intense research in this field, including clinical and radiological evaluations, genetic studies and investigations using model systems, the mechanism underlying GBA1-PD is still being pursued. Insights from this association have emphasized the role of lysosomal pathways in parkinsonism. Furthermore, different therapeutic strategies considered or developed for Gaucher disease can now inform drug development for PD. The association between the rare, monogenic lysosomal storage disorder Gaucher disease and Parkinson disease has provided insights into the pathogenesis of this far more common neurodegenerative disease. Here, Sidransky and colleagues review the knowledge gained from decades of Gaucher disease research and explore the relationship between GBA1 and parkinsonism.\",\"PeriodicalId\":19085,\"journal\":{\"name\":\"Nature Reviews Neurology\",\"volume\":\"20 9\",\"pages\":\"526-540\"},\"PeriodicalIF\":28.2000,\"publicationDate\":\"2024-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Reviews Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41582-024-00999-z\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41582-024-00999-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Gaucher disease provides a unique window into Parkinson disease pathogenesis
An exciting development in the field of neurodegeneration is the association between the rare monogenic disorder Gaucher disease and the common complex disorder Parkinson disease (PD). Gaucher disease is a lysosomal storage disorder resulting from an inherited deficiency of the enzyme glucocerebrosidase, encoded by GBA1, which hydrolyses the glycosphingolipids glucosylceramide and glucosylsphingosine. The observation of parkinsonism in a rare subgroup of individuals with Gaucher disease first directed attention to the role of glucocerebrosidase deficiency in the pathogenesis of PD. PD occurs more frequently in people heterozygous for Gaucher GBA1 mutations, and 3–25% of people with Parkinson disease carry a GBA1 variant. However, only a small percentage of individuals with GBA1 variants develop parkinsonism, suggesting that the penetrance is low. Despite over a decade of intense research in this field, including clinical and radiological evaluations, genetic studies and investigations using model systems, the mechanism underlying GBA1-PD is still being pursued. Insights from this association have emphasized the role of lysosomal pathways in parkinsonism. Furthermore, different therapeutic strategies considered or developed for Gaucher disease can now inform drug development for PD. The association between the rare, monogenic lysosomal storage disorder Gaucher disease and Parkinson disease has provided insights into the pathogenesis of this far more common neurodegenerative disease. Here, Sidransky and colleagues review the knowledge gained from decades of Gaucher disease research and explore the relationship between GBA1 and parkinsonism.
期刊介绍:
Nature Reviews Neurology aims to be the premier source of reviews and commentaries for the scientific and clinical communities we serve. We want to provide an unparalleled service to authors, referees, and readers, and we work hard to maximize the usefulness and impact of each article. The journal publishes Research Highlights, Comments, News & Views, Reviews, Consensus Statements, and Perspectives relevant to researchers and clinicians working in the field of neurology. Our broad scope ensures that the work we publish reaches the widest possible audience. Our articles are authoritative, accessible, and enhanced with clearly understandable figures, tables, and other display items. This page gives more detail about the aims and scope of the journal.