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Molecular therapy for polyQ disorders: from bench to clinical trials. 多 Q 疾病的分子疗法：从实验室到临床试验。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-09-01 Epub Date: 2024-06-04 DOI: 10.1016/j.molmed.2024.05.004
João de Sousa-Lourenço, Ana C Silva, Luís Pereira de Almeida, Rui J Nobre
{"title":"Molecular therapy for polyQ disorders: from bench to clinical trials.","authors":"João de Sousa-Lourenço, Ana C Silva, Luís Pereira de Almeida, Rui J Nobre","doi":"10.1016/j.molmed.2024.05.004","DOIUrl":"10.1016/j.molmed.2024.05.004","url":null,"abstract":"<p><p>Polyglutamine (polyQ) disorders are monogenic neurodegenerative disorders. Currently, no therapies are available for this complex group of disorders. Here, we aim to provide an overview of recent promising preclinical studies and the ongoing clinical trials focusing on molecular therapies for polyQ disorders.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"804-808"},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262081","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
Boosting endogenous dopamine production: a novel therapeutic approach for Parkinson's disease. 促进内源性多巴胺分泌：治疗帕金森病的新方法。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-09-01 Epub Date: 2024-06-25 DOI: 10.1016/j.molmed.2024.06.002
Erik H Douma, Marten P Smidt, Lars P van der Heide
{"title":"Boosting endogenous dopamine production: a novel therapeutic approach for Parkinson's disease.","authors":"Erik H Douma, Marten P Smidt, Lars P van der Heide","doi":"10.1016/j.molmed.2024.06.002","DOIUrl":"10.1016/j.molmed.2024.06.002","url":null,"abstract":"<p><p>Innovative therapeutic strategies are urgently needed for Parkinson's disease due to limited efficacy of current treatments and a weak therapeutic pipeline. In this forum article, we propose targeting tyrosine hydroxylase phosphorylation as a novel mechanism of action to address this critical need.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"800-803"},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459476","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
Pathogenic mechanisms in genetically defined Ehlers-Danlos syndromes. 基因定义的埃勒斯-丹洛斯综合征的致病机制。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-09-01 Epub Date: 2024-08-14 DOI: 10.1016/j.molmed.2024.06.001
Delfien Syx, Fransiska Malfait
{"title":"Pathogenic mechanisms in genetically defined Ehlers-Danlos syndromes.","authors":"Delfien Syx, Fransiska Malfait","doi":"10.1016/j.molmed.2024.06.001","DOIUrl":"10.1016/j.molmed.2024.06.001","url":null,"abstract":"<p><p>The Ehlers-Danlos syndromes (EDS) are a group of rare heritable connective tissue disorders, common hallmarks of which are skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Currently, 13 EDS types are recognized, caused by defects in 20 genes which consequently alter biosynthesis, organization, and/or supramolecular assembly of collagen fibrils in the extracellular matrix (ECM). Molecular analyses on patient samples (mostly dermal fibroblast cultures), combined with studies on animal models, have highlighted that part of EDS pathogenesis can be attributed to impaired cellular dynamics. Although our understanding of the full extent of (extra)cellular consequences is still limited, this narrative review aims to provide a comprehensive overview of our current knowledge on the extracellular, pericellular, and intracellular alterations implicated in EDS pathogenesis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"824-843"},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988988","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
The emerging role of ACOD1/itaconate pathway in atherosclerosis. ACOD1/itaconate 通路在动脉粥样硬化中的新作用。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-09-01 Epub Date: 2024-06-05 DOI: 10.1016/j.molmed.2024.05.015
Jingjing Xu, Suowen Xu
{"title":"The emerging role of ACOD1/itaconate pathway in atherosclerosis.","authors":"Jingjing Xu, Suowen Xu","doi":"10.1016/j.molmed.2024.05.015","DOIUrl":"10.1016/j.molmed.2024.05.015","url":null,"abstract":"<p><p>As an endogenous immunometabolite, itaconate has excellent anti-inflammatory effects. However, it remains unknown whether itaconate protects against atherosclerosis. Two recent studies, by Song et al. and Cyr et al., revealed the emerging role of the aconitate decarboxylase 1/itaconate pathway in atherosclerosis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"797-799"},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284855","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
HPV integration and cervical cancer: a failed evolutionary viral trait. HPV 整合与宫颈癌：进化失败的病毒特征。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-09-01 Epub Date: 2024-06-09 DOI: 10.1016/j.molmed.2024.05.009
Mariano A Molina, Renske D M Steenbergen, Anna Pumpe, Angelique N Kenyon, Willem J G Melchers
{"title":"HPV integration and cervical cancer: a failed evolutionary viral trait.","authors":"Mariano A Molina, Renske D M Steenbergen, Anna Pumpe, Angelique N Kenyon, Willem J G Melchers","doi":"10.1016/j.molmed.2024.05.009","DOIUrl":"10.1016/j.molmed.2024.05.009","url":null,"abstract":"<p><p>Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"890-902"},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296762","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
Neutrophils and extracellular traps in crystal-associated diseases. 晶体相关疾病中的中性粒细胞和细胞外捕获器。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-09-01 Epub Date: 2024-06-08 DOI: 10.1016/j.molmed.2024.05.010
Qiuyue Ma, Stefanie Steiger
{"title":"Neutrophils and extracellular traps in crystal-associated diseases.","authors":"Qiuyue Ma, Stefanie Steiger","doi":"10.1016/j.molmed.2024.05.010","DOIUrl":"10.1016/j.molmed.2024.05.010","url":null,"abstract":"<p><p>Crystalline material can cause a multitude of acute and chronic inflammatory diseases, such as gouty arthritis, silicosis, kidney disease, and atherosclerosis. Crystals of various types are thought to cause similar inflammatory responses, including the release of proinflammatory mediators and formation of neutrophil extracellular traps (NETs), processes that further promote necroinflammation and tissue damage. It has become apparent that the intensity of inflammation and the related mechanisms of NET formation and neutrophil death in crystal-associated diseases can vary depending on the crystal type, amount, and site of deposition. This review details new mechanistic insights into crystal biology, highlights the differential effects of various crystals on neutrophils and extracellular trap (ET) formation, and discusses treatment strategies and potential future approaches for crystal-associated disorders.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"809-823"},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296763","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
Emerging therapies in hereditary ataxias. 遗传性共济失调的新兴疗法。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-08-16 DOI: 10.1016/j.molmed.2024.07.008
Mallory L S Eisel, Matthew Burns, Tetsuo Ashizawa, Barry Byrne, Manuela Corti, Sub H Subramony
{"title":"Emerging therapies in hereditary ataxias.","authors":"Mallory L S Eisel, Matthew Burns, Tetsuo Ashizawa, Barry Byrne, Manuela Corti, Sub H Subramony","doi":"10.1016/j.molmed.2024.07.008","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.008","url":null,"abstract":"<p><p>Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets. In this review, we focus on Friedreich ataxia (FRDA) and the polyglutamine ataxias in which translational research is active. However, much remains to be done to identify safe and effective molecules, create ideal delivery methods, and perform innovative clinical trials to prove the safety and efficacy of treatments for these rare but devastating diseases.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996568","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
Subscription and Copyright Information 订阅和版权信息
IF 13.6 1区 医学
Trends in molecular medicine Pub Date : 2024-08-14 DOI: 10.1016/s1471-4914(24)00201-6
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s1471-4914(24)00201-6","DOIUrl":"https://doi.org/10.1016/s1471-4914(24)00201-6","url":null,"abstract":"No Abstract","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"2 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220404","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 : 2024-08-14 DOI: 10.1016/s1471-4914(24)00198-9
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/s1471-4914(24)00198-9","DOIUrl":"https://doi.org/10.1016/s1471-4914(24)00198-9","url":null,"abstract":"No Abstract","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"5 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220405","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.
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-08-01 Epub Date: 2024-07-23 DOI: 10.1016/j.molmed.2024.06.013
Boris Cheval, Yohannes Gemechu, Parastoo Shahrouzi, Liye Zou
{"title":"Science around the world.","authors":"Boris Cheval, Yohannes Gemechu, Parastoo Shahrouzi, Liye Zou","doi":"10.1016/j.molmed.2024.06.013","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.06.013","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"30 8","pages":"699-701"},"PeriodicalIF":12.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795203","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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