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LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting. 帕金森病中的 LRRK2：上游调控和靶向治疗。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-08-16 DOI: 10.1016/j.molmed.2024.07.003
Yulan Xiong, Jianzhong Yu
{"title":"LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.","authors":"Yulan Xiong, Jianzhong Yu","doi":"10.1016/j.molmed.2024.07.003","DOIUrl":"10.1016/j.molmed.2024.07.003","url":null,"abstract":"<p><p>Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of Parkinson's disease (PD) to date. Dysfunction in LRRK2 enzymatic activities and elevated protein levels are associated with the disease. How is LRRK2 activated, and what downstream molecular and cellular processes does LRRK2 regulate? Addressing these questions is crucial to decipher the disease mechanisms. In this review we focus on the upstream regulations and briefly discuss downstream substrates of LRRK2 as well as the cellular consequences caused by these regulations. Building on these basic findings, we discuss therapeutic strategies targeting LRRK2 and highlight the challenges in clinical trials. We further highlight the important questions that remains to be answered in the LRRK2 field.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"982-996"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Naked mole-rats: at the heart of it. 裸体鼹鼠：核心所在。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-05-29 DOI: 10.1016/j.molmed.2024.05.008
Claudie Gabillard-Lefort, Jeanne Mialet-Perez, Guy Lenaers, Olivier R Baris
{"title":"Naked mole-rats: at the heart of it.","authors":"Claudie Gabillard-Lefort, Jeanne Mialet-Perez, Guy Lenaers, Olivier R Baris","doi":"10.1016/j.molmed.2024.05.008","DOIUrl":"10.1016/j.molmed.2024.05.008","url":null,"abstract":"<p><p>Faulkes et al. recently showed that naked mole-rats (NMRs) have a very distinctive cardiac gene expression profile among other African mole-rats, as well as metabolic variations that result from their chronic exposure to a hypoxic environment. These adaptations might underlie their resistance to cardiac ischemic injuries.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"906-907"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vaccine-based immunotherapy and related preclinical models for glioma. 基于疫苗的胶质瘤免疫疗法及相关临床前模型。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-07-15 DOI: 10.1016/j.molmed.2024.06.009
Longping Yao, Maryam Hatami, Wenbin Ma, Thomas Skutella
{"title":"Vaccine-based immunotherapy and related preclinical models for glioma.","authors":"Longping Yao, Maryam Hatami, Wenbin Ma, Thomas Skutella","doi":"10.1016/j.molmed.2024.06.009","DOIUrl":"10.1016/j.molmed.2024.06.009","url":null,"abstract":"<p><p>Glioma, the most common primary malignant tumor in the central nervous system (CNS), lacks effective treatments, and >60% of cases are glioblastoma (GBM), the most aggressive form. Despite advances in immunotherapy, GBM remains highly resistant. Approaches that target tumor antigens expedite the development of immunotherapies, including personalized tumor-specific vaccines, patient-specific target selection, dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. Recent studies show promising results in treating GBM and lower-grade glioma (LGG), fostering hope for future immunotherapy. This review discusses tumor vaccines against glioma, preclinical models in immunological research, and the role of CD4<sup>+</sup> T cells in vaccine-induced antitumor immunity. We also summarize clinical approaches, challenges, and future research for creating more effective vaccines.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"965-981"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insights from HIV-1 vaccine and passive immunization efficacy trials. 从 HIV-1 疫苗和被动免疫疗效试验中获得的启示。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-06-18 DOI: 10.1016/j.molmed.2024.05.017
Shamim Ahmed, Alon Herschhorn
{"title":"Insights from HIV-1 vaccine and passive immunization efficacy trials.","authors":"Shamim Ahmed, Alon Herschhorn","doi":"10.1016/j.molmed.2024.05.017","DOIUrl":"10.1016/j.molmed.2024.05.017","url":null,"abstract":"<p><p>An effective HIV-1 vaccine is still not available, and most vaccine efficacy trials conducted over the years resulted in no significant overall protection. Here we highlight several insights gained from these trials as well as emerging questions that may be important for further guidance to advance current research directions.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"908-912"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nontraditional models as research tools: the road not taken. 作为研究工具的非传统模型：没有走过的路。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-07-27 DOI: 10.1016/j.molmed.2024.07.005
Hippokratis Kiaris
{"title":"Nontraditional models as research tools: the road not taken.","authors":"Hippokratis Kiaris","doi":"10.1016/j.molmed.2024.07.005","DOIUrl":"10.1016/j.molmed.2024.07.005","url":null,"abstract":"<p><p>Historical reasons resulted in the almost exclusive use of a few species, most prominently Mus musculus, as the mainstream models in biomedical research. This selection was not based on Mus's distinctive relevance to human disease but rather to the pre-existing availability of resources and tools for the species that were used as models, which has enabled their adoption for research in health sciences. Unless the utilization and range of nontraditional research models expand considerably, progress in biomedical research will remain restricted within the trajectory that has been set by the existing models and their ability to provide clinically relevant information.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"924-931"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The trio of circadian clock, intestinal flora, and cancer 昼夜节律、肠道菌群和癌症三重奏
IF 13.6 1区 医学
Trends in molecular medicine Pub Date : 2024-09-19 DOI: 10.1016/j.molmed.2024.09.001
Weici Liu, Zheshun Pi, Wenjun Mao
{"title":"The trio of circadian clock, intestinal flora, and cancer","authors":"Weici Liu, Zheshun Pi, Wenjun Mao","doi":"10.1016/j.molmed.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.001","url":null,"abstract":"<p>Dysbiotic intestinal flora and a disrupted circadian clock are intimately related to cancer biological behaviors, yet their interwoven regulatory mechanisms remain an explorative field. Studies by <span><span>Ren <em>et al</em>.</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> and <span><span>Liu <em>et al</em>.</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> provide deeper insights into the potential roles of intestinal flora and the circadian clock in colorectal tumorigenesis and lung metastasis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"14 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fibrodysplasia ossificans progressiva emerges from obscurity 渐进性骨纤维增生症从默默无闻中崭露头角
IF 13.6 1区 医学
Trends in molecular medicine Pub Date : 2024-09-18 DOI: 10.1016/j.molmed.2024.08.010
Frederick S. Kaplan, Eileen M. Shore, Robert J. Pignolo
{"title":"Fibrodysplasia ossificans progressiva emerges from obscurity","authors":"Frederick S. Kaplan, Eileen M. Shore, Robert J. Pignolo","doi":"10.1016/j.molmed.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.08.010","url":null,"abstract":"<p>Fibrodysplasia ossificans progressiva (FOP), a disorder of congenital skeletal malformations and progressive extraskeletal ossification, is the most severe form of heterotopic ossification (HO) in humans. Gain-of-function pathogenic variants in activin A receptor type I (ACVR1), a bone morphogenetic protein (BMP) type 1 receptor, cause FOP by dramatically altering the normal physiologic functions of ACVR1, impacting BMP signaling and other interacting pathways. These alterations affect various systems, including inflammation, innate immunity, hypoxia sensing, wound healing, aging, temperature and mechanical thresholds, pain sensitivity, skeletal growth, diarthrodial joint patterning, joint function and fate, and HO. This article examines the emergent properties of FOP’s diverse phenotypes, proposes a schema for targeting these phenotypes, and highlights outstanding questions and knowledge gaps.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"26 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incorporating placental pathology into clinical care and research 将胎盘病理学纳入临床护理和研究中
IF 13.6 1区 医学
Trends in molecular medicine Pub Date : 2024-09-18 DOI: 10.1016/j.molmed.2024.08.002
Drucilla Roberts, Omonigho Aisagbonhi, Mana M. Parast
{"title":"Incorporating placental pathology into clinical care and research","authors":"Drucilla Roberts, Omonigho Aisagbonhi, Mana M. Parast","doi":"10.1016/j.molmed.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.08.002","url":null,"abstract":"<p>Despite recent standardization of placental evaluation and establishment of criteria for diagnosis of major patterns of placental injury, placental pathological examination remains undervalued and under-utilized. The placenta can harbor a significant amount of information relevant to both the pregnant person and offspring. Placental pathology can also provide a significant context for pathophysiological study of adverse pregnancy outcomes, helping to optimally subcategorize the ‘great obstetric syndromes’ of pre-eclampsia (PE), spontaneous preterm birth (sPTB), and fetal growth restriction (FGR), and to identify causes of stillbirth. We hereby propose that placental evaluation should be incorporated into routine delivery of obstetric and neonatal care, and further suggest that its integration into clinical, translational, and basic research could significantly advance our understanding of pregnancy complications and adverse neonatal outcomes.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"29 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Science around the world 世界各地的科学
IF 13.6 1区 医学
Trends in molecular medicine Pub Date : 2024-09-18 DOI: 10.1016/j.molmed.2024.08.009
Olivier R. Baris, Alon Herschhorn, Yulan Xiong
{"title":"Science around the world","authors":"Olivier R. Baris, Alon Herschhorn, Yulan Xiong","doi":"10.1016/j.molmed.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.08.009","url":null,"abstract":"No Abstract","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"24 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 13.6 1区 医学
Trends in molecular medicine Pub Date : 2024-09-11 DOI: 10.1016/s1471-4914(24)00226-0
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/s1471-4914(24)00226-0","DOIUrl":"https://doi.org/10.1016/s1471-4914(24)00226-0","url":null,"abstract":"No Abstract","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"4 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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