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Neurotransmitter-activated GPCR signaling in myelin plasticity. 髓鞘可塑性中的神经递质激活GPCR信号。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-05-06 DOI: 10.1016/j.molmed.2026.04.005
Marta Cimadevila, Carlos Matute
{"title":"Neurotransmitter-activated GPCR signaling in myelin plasticity.","authors":"Marta Cimadevila, Carlos Matute","doi":"10.1016/j.molmed.2026.04.005","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.04.005","url":null,"abstract":"<p><p>Myelination is increasingly recognized as a dynamic and adaptive process regulated by oligodendrocytes throughout life. Beyond providing electrical insulation, myelin supports axonal metabolism and may serve as an energy reservoir under metabolic stress, highlighting the importance of physiological myelin turnover. Dysregulation of myelin dynamics contributes to a wide spectrum of neurological disorders, including demyelinating, neurodegenerative, and neuropsychiatric diseases. Growing evidence indicates that neurotransmitter signaling through G protein-coupled receptors (GPCRs) expressed by oligodendrocyte lineage cells regulates myelin formation, remodeling, and repair. In this review, we discuss how neurotransmitter-activated GPCRs control oligodendrocyte function and myelin plasticity, and we explore their potential as targets to promote myelin regeneration and restore neural circuit function.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843105","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
Erythroid-hormonal axis in long COVID. 长冠状体的红激素轴。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-05-04 DOI: 10.1016/j.molmed.2026.04.006
Shokrollah Elahi
{"title":"Erythroid-hormonal axis in long COVID.","authors":"Shokrollah Elahi","doi":"10.1016/j.molmed.2026.04.006","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.04.006","url":null,"abstract":"<p><p>Long COVID may reflect a failure of coordinated physiological recovery rather than persistent infection. Emerging evidence identifies inflammation-driven disruption of erythropoiesis and hormonal balance as central mechanisms linking immune dysregulation, metabolic stress, and persistent symptoms. This framework positions erythroid-endocrine pathways as key determinants of recovery and promising therapeutic targets.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843063","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
Targeting the NAD+-PARP1-XRCC1 axis in ALS. 在ALS中靶向NAD+-PARP1-XRCC1轴。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-05-04 DOI: 10.1016/j.molmed.2026.04.004
Md Ibrahim, Md Shahadat Hossain, Lezanne Ooi, Md Mahmudul Hasan, Shandra Ahsan, Aliasger K Salem, Gary A Piazza, Xiaodong Feng, Fakhrul Ahsan
{"title":"Targeting the NAD<sup>+</sup>-PARP1-XRCC1 axis in ALS.","authors":"Md Ibrahim, Md Shahadat Hossain, Lezanne Ooi, Md Mahmudul Hasan, Shandra Ahsan, Aliasger K Salem, Gary A Piazza, Xiaodong Feng, Fakhrul Ahsan","doi":"10.1016/j.molmed.2026.04.004","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.04.004","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) remains a fatal neurodegenerative disease with few effective therapies. Emerging evidence indicates that oxidative DNA damage, defective base excision and single-strand break repair, and progressive NAD<sup>+</sup> depletion contribute to motor neuron degeneration. The NAD<sup>+</sup>-PARP1-XRCC1 axis sits at the intersection of genome maintenance and metabolic control, linking DNA damage signaling to cellular bioenergetics. When dysregulated, this pathway may drive persistent PARP1 activation, failed repair, and energetic collapse. In this review, we integrate mechanistic and translational evidence supporting this axis as a therapeutic target in ALS. We propose a staged translational framework that prioritizes repurposable low-trapping PARP1 inhibitors combined with NAD<sup>+</sup> support, followed by central nervous system-directed RNA-lipid nanoparticle delivery of repair factors, with poly(ADP-ribose) and NAD<sup>+</sup> metabolites as pharmacodynamic biomarkers.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843060","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
Mitochondrial dysfunction in cerebrovascular diseases. 脑血管疾病的线粒体功能障碍。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-04-30 DOI: 10.1016/j.molmed.2026.04.002
Fabio Marcheggiani, Ilaria Nunzi, Loredana Rao, Nada Dhaouadi, Salvatore Nesci, Paolo Pinton, Saverio Marchi
{"title":"Mitochondrial dysfunction in cerebrovascular diseases.","authors":"Fabio Marcheggiani, Ilaria Nunzi, Loredana Rao, Nada Dhaouadi, Salvatore Nesci, Paolo Pinton, Saverio Marchi","doi":"10.1016/j.molmed.2026.04.002","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.04.002","url":null,"abstract":"<p><p>Mitochondria are central regulators of cerebrovascular health through their control of energy metabolism, Ca<sup>2+</sup> homeostasis, and redox signaling, and their dysfunction represents a convergent pathogenic mechanism across cerebrovascular diseases. In ischemic stroke, mitochondrial failure exacerbates neuronal injury via permeability transition pore opening, oxidative stress, and bioenergetic collapse, while altered mitochondrial dynamics and the release of mitochondrial damage-associated molecular patterns amplify neuroinflammation during reperfusion. Beyond stroke, mitochondrial dysfunction contributes to intracranial aneurysms, atherosclerotic stenosis, and vascular malformations, where oxidative stress, mitochondrial DNA instability, and cell type-specific metabolic reprogramming drive vascular remodeling and lesion progression. In this review, we integrate recent evidence highlighting context- and stage-dependent roles of mitochondria in cerebrovascular pathology and discuss implications for biomarker discovery, therapeutic targeting, and translational strategies.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821094","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
Epigenetic remodeling after viral pneumonia accelerates lung tumorigenesis. 病毒性肺炎后的表观遗传重塑加速肺肿瘤发生。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-04-25 DOI: 10.1016/j.molmed.2026.04.003
Weici Laurence Liu, Zheshun Pi, Peng Luo, Wenjun Mao
{"title":"Epigenetic remodeling after viral pneumonia accelerates lung tumorigenesis.","authors":"Weici Laurence Liu, Zheshun Pi, Peng Luo, Wenjun Mao","doi":"10.1016/j.molmed.2026.04.003","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.04.003","url":null,"abstract":"<p><p>Previous epidemiological studies have associated viral pneumonia with an increased risk of lung cancer. Recently, Qian et al. revealed that epigenetic reprogramming following respiratory viral infections accelerates tumorigenesis by orchestrating a protumor microenvironment, providing mechanistic insights and potential therapeutic strategies for intercepting lung cancer progression after viral pneumonia.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782121","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
Tick-borne encephalitis: emerging clinical trends and challenges. 蜱传脑炎：新的临床趋势和挑战。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-04-17 DOI: 10.1016/j.molmed.2026.03.002
Karin Byskata, Sofia Bartholdsson, Sara Gredmark-Russ
{"title":"Tick-borne encephalitis: emerging clinical trends and challenges.","authors":"Karin Byskata, Sofia Bartholdsson, Sara Gredmark-Russ","doi":"10.1016/j.molmed.2026.03.002","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.03.002","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718059","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
β-hydroxybutyrate supplementation boosts the tumor-killing potential of CAR T cells. 补充β-羟基丁酸可增强CAR - T细胞的肿瘤杀伤潜力。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-04-14 DOI: 10.1016/j.molmed.2026.04.001
Christos Adamopoulos, Kostas A Papavassiliou, Athanasios G Papavassiliou
{"title":"β-hydroxybutyrate supplementation boosts the tumor-killing potential of CAR T cells.","authors":"Christos Adamopoulos, Kostas A Papavassiliou, Athanasios G Papavassiliou","doi":"10.1016/j.molmed.2026.04.001","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.04.001","url":null,"abstract":"<p><p>In a recent study in Cell, Liu et al. identify β-hydroxybutyrate as a practical metabolic adjuvant for CAR-T cells. By fueling the TCA cycle and reshaping transcriptional and epigenetic programs, this ketone body enhances proliferation, persistence, and tumor control, suggesting that metabolic supplementation may offer a simple route to more effective adoptive immunotherapy.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692396","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
Creutzfeldt-Jakob disease is an Alzheimer's disease-related dementia. 克雅氏病是一种与阿尔茨海默病相关的痴呆症。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-04-14 DOI: 10.1016/j.molmed.2026.03.009
Joel C Watts, Christina J Sigurdson, Debbie Yobs, Claudio Soto
{"title":"Creutzfeldt-Jakob disease is an Alzheimer's disease-related dementia.","authors":"Joel C Watts, Christina J Sigurdson, Debbie Yobs, Claudio Soto","doi":"10.1016/j.molmed.2026.03.009","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.03.009","url":null,"abstract":"<p><p>Neurodegenerative dementias are debilitating diseases that include Alzheimer's disease (AD) and AD-related dementias (ADRDs). Creutzfeldt-Jakob disease (CJD) is a rapidly progressive dementia caused by the accumulation of prions in the brain. Despite the many similarities between CJD and the ADRDs, CJD is currently not included in the ADRD group. In this opinion article, we discuss the significant impact of prion research on our understanding of the molecular pathogenesis of ADRDs as well as on the development of diagnostic tests and therapeutic strategies. We argue that CJD should be included in the group of ADRDs to enhance research cooperation and accelerate understanding of underlying disease mechanisms toward the goal of developing effective therapies to slow neurodegeneration.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692351","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
Targeting the hyaluronic acid-CD44 axis in hepatocellular carcinoma. 靶向肝细胞癌透明质酸- cd44轴。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-04-11 DOI: 10.1016/j.molmed.2026.03.008
Georgia Zancotti, Gisela Weiz, Cyrollah Disoma, Claudio Tiribelli, Caecilia Sukowati
{"title":"Targeting the hyaluronic acid-CD44 axis in hepatocellular carcinoma.","authors":"Georgia Zancotti, Gisela Weiz, Cyrollah Disoma, Claudio Tiribelli, Caecilia Sukowati","doi":"10.1016/j.molmed.2026.03.008","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.03.008","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a major global health challenge, with rising incidence, frequent development of drug resistance, and limited long-term survival despite advances in systemic therapies. Within the tumor microenvironment, the interaction between hyaluronic acid (HA) and cluster of differentiation 44 (CD44) is linked to tumor progression and therapeutic failure. Accordingly, targeting the HA-CD44 signaling axis represents a promising strategy to overcome resistance. This review highlights potential approaches, including inhibition of HA synthesis, enzymatic HA degradation, CD44 blockade, and HA-based nanocarriers for selective drug delivery, alone or combined with existing therapies. Leveraging HA-CD44 biology may help refine profiling and support the development of more personalized treatments, ultimately enhancing outcomes for HCC patients.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677026","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
Thymus regeneration therapies: entering a new era. 胸腺再生疗法：进入新时代。
IF 13.8 1区 医学
Trends in molecular medicine Pub Date : 2026-04-10 DOI: 10.1016/j.molmed.2026.03.005
Alexandra Y Kreins, Katja G Weinacht
{"title":"Thymus regeneration therapies: entering a new era.","authors":"Alexandra Y Kreins, Katja G Weinacht","doi":"10.1016/j.molmed.2026.03.005","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.03.005","url":null,"abstract":"<p><p>The function of the thymus, essential for T cell development, declines sharply with age. Genetic defects that disrupt thymic organogenesis or function lead to profound immunodeficiency and autoimmunity. Allogeneic thymus transplantation for congenital athymia, the only existing thymus replacement therapy, provides proof of concept for T cell reconstitution but remains constrained by donor availability and Human Leukocyte Antigen (HLA) mismatch. Advances in single-cell biology and stem cell engineering now make scalable thymus regeneration an attainable goal. In particular, induced pluripotent stem cell-derived thymic epithelial cells could restore endogenous T cell development and immune tolerance in an HLA-compatible manner. We propose that the thymus is uniquely suited for stem cell-based regeneration, with the potential to transform the treatment of immune deficiency, transplantation, cancer, autoimmunity, and aging itself.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676983","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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