{"title":"帕金森病相关富亮氨酸重复激酶2 (LRRK2)的结构生物学研究","authors":"Andres E. Leschziner","doi":"10.1016/j.jbc.2025.110376","DOIUrl":null,"url":null,"abstract":"Leucine Rich Repeat Kinase 2 (LRRK2) has gone, in a little over two decades, from a novel gene linked to cases of Parkinson’s Disease (PD) in one family to being the main actionable target for PD therapeutics, with several clinical trials targeting it currently underway. While much remains to be understood about LRRK2—including, chiefly, why its increased activity is linked to PD—much has also been learned. One of the areas where our knowledge has increased exponentially in a very short time is the structural biology of LRRK2. The goal of this review is to provide a survey of the current landscape of LRRK2 structural biology with an emphasis on the functional insights that structures have provided.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"25 1","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Structural biology of Parkinson’s Disease-associated Leucine-Rich Repeat Kinase 2 (LRRK2)\",\"authors\":\"Andres E. Leschziner\",\"doi\":\"10.1016/j.jbc.2025.110376\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Leucine Rich Repeat Kinase 2 (LRRK2) has gone, in a little over two decades, from a novel gene linked to cases of Parkinson’s Disease (PD) in one family to being the main actionable target for PD therapeutics, with several clinical trials targeting it currently underway. While much remains to be understood about LRRK2—including, chiefly, why its increased activity is linked to PD—much has also been learned. One of the areas where our knowledge has increased exponentially in a very short time is the structural biology of LRRK2. The goal of this review is to provide a survey of the current landscape of LRRK2 structural biology with an emphasis on the functional insights that structures have provided.\",\"PeriodicalId\":15140,\"journal\":{\"name\":\"Journal of Biological Chemistry\",\"volume\":\"25 1\",\"pages\":\"\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-06-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biological Chemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jbc.2025.110376\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biological Chemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jbc.2025.110376","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Structural biology of Parkinson’s Disease-associated Leucine-Rich Repeat Kinase 2 (LRRK2)
Leucine Rich Repeat Kinase 2 (LRRK2) has gone, in a little over two decades, from a novel gene linked to cases of Parkinson’s Disease (PD) in one family to being the main actionable target for PD therapeutics, with several clinical trials targeting it currently underway. While much remains to be understood about LRRK2—including, chiefly, why its increased activity is linked to PD—much has also been learned. One of the areas where our knowledge has increased exponentially in a very short time is the structural biology of LRRK2. The goal of this review is to provide a survey of the current landscape of LRRK2 structural biology with an emphasis on the functional insights that structures have provided.
期刊介绍:
The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.