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  • Priming the Proteasome to Protect against Proteotoxicity
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-26
    Xuejun Wang; Hongmin Wang

    Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity

  • Therapeutic Manipulation of mtDNA Heteroplasmy: A Shifting Perspective
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-26
    Christopher B. Jackson; Doug M. Turnbull; Michal Minczuk; Payam A. Gammage

    Mutations of mitochondrial DNA (mtDNA) often underlie mitochondrial disease, one of the most common inherited metabolic disorders. Since the sequencing of the human mitochondrial genome and the discovery of pathogenic mutations in mtDNA more than 30 years ago, a movement towards generating methods for robust manipulation of mtDNA has ensued, although with relatively few advances and some controversy

  • Type 2 Diabetes Mellitus Drugs for Alzheimer’s Disease: Current Evidence and Therapeutic Opportunities
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-23
    Lei Meng; Xin-Yu Li; Liang Shen; Hong-Fang Ji

    Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) represent two major health burdens with steadily increasing prevalence and accumulating evidence indicates a close relationship between the two disorders. In view of their similar pathogenesis, the potential of T2DM drugs for the treatment of AD has attracted considerable attention in recent years, with inspiring outcomes. Here, we provide

  • Haptoglobin Therapeutics and Compartmentalization of Cell-Free Hemoglobin Toxicity
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-21
    Paul W. Buehler; Rok Humar; Dominik J. Schaer

    Hemolysis and accumulation of cell-free hemoglobin (Hb) in the circulation or in confined tissue compartments such as the subarachnoid space is an important driver of disease. Haptoglobin is the Hb binding and clearance protein in human plasma and an efficient antagonist of Hb toxicity resulting from physiological red blood cell turnover. However, endogenous concentrations of haptoglobin are insufficient

  • COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-21
    Jiumeng Sun; Wan-Ting He; Lifang Wang; Alexander Lai; Xiang Ji; Xiaofeng Zhai; Gairu Li; Marc A. Suchard; Jin Tian; Jiyong Zhou; Michael Veit; Shuo Su

    The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/

  • NIRF Nanoprobes for Cancer Molecular Imaging: Approaching Clinic
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-18
    Zhenhua Hu; Wen-Hua Chen; Jie Tian; Zhen Cheng

    Near-IR fluorescence imaging (NIRFI) is a highly promising technique for improving cancer theranostics in the era of precision medicine. Through the combination with cutting-edge bionanotechnologies, the potential of NIRFI can be greatly broadened. A variety of novel NIRF nanoprobes has been developed with ultimate goals of addressing unmet medical needs. Here, we present recent breakthroughs on the

  • Noncoding RNAs versus Protein Biomarkers in Cardiovascular Disease
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-12
    Christian Schulte; Temo Barwari; Abhishek Joshi; Tanja Zeller; Manuel Mayr

    The development of more sensitive protein biomarker assays results in continuous improvements in detectability, extending the range of clinical applications to the detection of subclinical cardiovascular disease (CVD). However, these efforts have not yet led to improvements in risk assessment compared with existing risk scores. Noncoding RNAs (ncRNAs) have been assessed as biomarkers, and miRNAs have

  • Development of Humanized Ossicles: Bridging the Hematopoietic Gap
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-03-03
    Steven J. Dupard; Ani Grigoryan; Stephanie Farhat; Daniel L. Coutu; Paul E. Bourgine

    Ectopic 'humanized ossicles' (hOss) are miniaturized, engineered human bone organs in mice displaying a similar structure and function to native mouse bones. However, they are composed of human mesenchymal derived cells forming a humanized bone marrow niche. This in vivo reconstitution of human skeletal and hematopoietic compartments provides an opportunity to investigate the cellular and molecular

  • Noncoding RNAs Controlling Telomere Homeostasis in Senescence and Aging
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-28
    Martina Rossi; Myriam Gorospe

    Aging is a universal and time-dependent biological decline associated with progressive deterioration of cells, tissues, and organs. Age-related decay can eventually lead to pathology such as cardiovascular and neurodegenerative diseases, cancer, and diabetes. A prominent molecular process underlying aging is the progressive shortening of telomeres, the structures that protect the ends of chromosomes

  • Assessing Toxicity with Human Cell-Based In Vitro Methods
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-22
    Daniele Zink; Jacqueline Kai Chin Chuah; Jackie Y. Ying

    In toxicology, there is a strong push towards replacing animal experiments with alternative methods, which include cell-based in vitro methods for the assessment of adverse health effects in humans. High-throughput methods are of central interest due to the large and steadily growing numbers of compounds that require assessment. Tremendous progress has been made during the last decade in developing

  • Bacterial Peptidoglycan as a Driver of Chronic Brain Inflammation
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-21
    Jon D. Laman; Bert A. ’t Hart; Christopher Power; Roman Dziarski

    Peptidoglycan (PGN) is a cell wall component of both Gram-positive and Gram-negative bacteria. Signature fragments of PGN are proinflammatory through engagement of pattern recognition receptors (PRR) on resident tissue cells and circulating leukocytes. Despite its abundance in the gut microbiota, there is limited recognition that PGN could contribute to chronic neuroinflammation. This review highlights

  • A lncRNA Decoy Predicts Sensitivity to Cisplatin
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-18
    Raquel Boque-Sastre; Sonia Guil

    In a recent iScience paper by Fan et al., the long noncoding (lnc)RNA CISAL is shown to form a DNA–RNA triplex and to directly regulate BRCA1 transcription, thereby increasing cisplatin sensitivity and serving as a treatment efficacy biomarker. This opens promising avenues of research from both mechanistic and translational perspectives.

  • The Centrosome Linker and Its Role in Cancer and Genetic Disorders
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-18
    Andrea Remo; Xue Li; Elmar Schiebel; Massimo Pancione

    Centrosome cohesion, the joining of the two centrosomes of a cell, is increasingly appreciated as a major regulator of cell functions such as Golgi organization and cilia positioning. One major element of centrosome cohesion is the centrosome linker that consists of a growing number of proteins. The timely disassembly of the centrosome linker enables centrosomes to separate and assemble a functional

  • Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-17
    Alyse L. Frisbee; William A. Petri

    Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated

  • Cell-Free DNA and Apoptosis: How Dead Cells Inform About the Living
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-17
    Ellen Heitzer; Lisa Auinger; Michael R. Speicher

    Cell-free DNA (cfDNA) is evolving into a widely used prognostic and predictive biomarker, particularly in oncology. However, its versatile clinical use precedes a profound understanding of the underlying biology of cfDNA release. There is much evidence to suggest that cfDNA is mainly derived from dying (i.e., apoptotic) cells. However, numerous cancer studies have shown that cfDNA is informative about

  • Transcription Factor Inhibition: Lessons Learned and Emerging Targets
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-15
    Andrew Chen; Angela N. Koehler

    Transcription factors have roles at focal points in signaling pathways, controlling many normal cellular processes, such as cell growth and proliferation, metabolism, apoptosis, immune responses, and differentiation. Their activity is frequently deregulated in disease and targeting this class of proteins is a major focus of interest. However, the structural disorder and lack of binding pockets have

  • Vaccination against Allergy: A Paradigm Shift?
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-13
    Martin F. Bachmann; Mona O. Mohsen; Matthias F. Kramer; Matthew D. Heath

    Since the discovery that IgE antibodies mediate allergy, decades of research have unraveled complex mechanisms associated with conventional immunotherapy and the vital protagonists that shape ‘immune tolerance’ to allergens. Debate exists on what should constitute the dominant effector mechanism in driving rational drug designs for next-generation immunotherapies. As vaccine technology continues to

  • Tumor Progression of Breast Cancer during Hyperinsulinemic Obesity
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-13
    Austin C. Boese; Sumin Kang

    Factors of metabolic syndrome including hyperinsulinemia and obesity are well known to increase the risk of cancer incidence and progression. In a recent iScience article, Ramos et al. demonstrate a novel tumor-suppressor role of the circadian transcription factor BMAL1 in triple-negative breast cancer (TNBC) specifically under conditions of hyperinsulinemia.

  • Targeted Avenues for Cancer Treatment: The MEK5–ERK5 Signaling Pathway
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-13
    Diane M. Pereira; Cecília M.P. Rodrigues

    Twenty years have passed since extracellular signal-regulated kinase 5 (ERK5) and its upstream activator, mitogen-activated protein kinase 5 (MEK5), first emerged onto the cancer research scene. Although we have come a long way in defining the liaison between dysregulated MEK5–ERK5 signaling and the pathogenesis of epithelial and nonepithelial malignancies, selective targeting of this unique pathway

  • Heart Failure and Adipose Mesenchymal Stem Cells
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-12
    Kenichi Matsushita

    Mesenchymal stem cells (MSCs) are considered a promising cell type for the treatment of heart failure (HF). In particular, MSCs in adipose tissue are being evaluated as an effective therapeutic tool. However, adipose MSCs are a major source of adipocyte generation and linked to obesity, which is an independent risk factor for HF. MSCs express all of the components of the renin–angiotensin system (RAS)

  • Chemical Chaperones as Novel Drugs for Parkinson’s Disease
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-12
    Jordi Pujols; Samuel Peña-Díaz; Irantzu Pallarès; Salvador Ventura

    Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons and the accumulation of deposits of α-synuclein (α-syn) in the brain. The pivotal role of α-syn aggregation in PD makes it an attractive target for potential disease-modifying therapies. However, the disordered nature of the protein, its multistep aggregation mechanism, and the lack of structural information on intermediate

  • Only 20-25% Deuteration of Polyunsaturated Fatty Acids Prevents Lipid Peroxidation.
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-02-04
    Paldeep S Atwal,Mark Midei,Peter Milner

  • Do Two Mitochondrial Wrongs Help Make Cells Right?
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-12-05
    Ajit S Divakaruni,Anne N Murphy

    Using an unbiased genetic screen, To et al. map genes that enhance or suppress growth defects in response to different mitochondrial inhibitors to model mitochondrial disease. The findings have novel implications for the interconnectivity of bioenergetic pathways, and suggest a provocative strategy to treat primary mitochondrial disorders.

  • Glutamine Skipping the Q into Mitochondria.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-12-02
    Zachary E Stine,Chi V Dang

    Imported across the plasma membrane by SLC1A5, glutamine has emerged as a metabolic fuel that is catabolized by mitochondrial glutaminase to support tumor growth. The missing link between cytoplasmic and mitochondrial glutamine metabolism is now provided by Yoo et al., identifying the mitochondrial glutamine importer as a variant of SLC1A5.

  • Regulation of Mitochondrial ATP Production: Ca2+ Signaling and Quality Control.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-22
    Liron Boyman,Mariusz Karbowski,W Jonathan Lederer

    Cardiac ATP production primarily depends on oxidative phosphorylation in mitochondria and is dynamically regulated by Ca2+ levels in the mitochondrial matrix as well as by cytosolic ADP. We discuss mitochondrial Ca2+ signaling and its dysfunction which has recently been linked to cardiac pathologies including arrhythmia and heart failure. Similar dysfunction in other excitable and long-lived cells

  • Drug Development for the Therapy of Mitochondrial Diseases.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-11
    Volkmar Weissig

    Mitochondrial diseases are a heterogeneous group of inherited or acquired devastating disorders that affect the energy metabolism of the body. Many strategies have been investigated, but currently there is no FDA-approved drug that can alleviate disease symptoms or slow disease progression. This review analyzes to what extent growing knowledge over the past two decades about the etiology and pathogenesis

  • Mitochondria-Lysosome Crosstalk: From Physiology to Neurodegeneration.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-29
    Cláudia M Deus,King Faisal Yambire,Paulo J Oliveira,Nuno Raimundo

    Cellular function requires coordination between different organelles and metabolic cues. Mitochondria and lysosomes are essential for cellular metabolism as major contributors of chemical energy and building blocks. It is therefore pivotal for cellular function to coordinate the metabolic roles of mitochondria and lysosomes. However, these organelles do more than metabolism, given their function as

  • Mitochondrial Defects Drive Degenerative Retinal Diseases.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-23
    Deborah A Ferrington,Cody R Fisher,Renu A Kowluru

    Mitochondrial dysfunction is involved in the pathology of two major blinding retinal diseases, diabetic retinopathy (DR) and age-related macular degeneration (AMD). These diseases accumulate mitochondrial defects in distinct retinal subcellular structures, the vascular/neural network in DR and the retinal pigment epithelium (RPE) in AMD. These mitochondrial defects cause a metabolic crisis that drives

  • Human Narratives in Science: The Power of Storytelling.
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-01-29
    Fanuel J Muindi,Lakshmi Ramachandran,Jessica W Tsai

    Science is fundamentally about people - the people who do science and the people who are affected by science. However, access to these human stories is limited. We argue that these narratives must be captured and shared publicly as an integral part of the scientific process.

  • Cardiac Glycosides as Senolytic Compounds.
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-01-23
    Nadine Martin,Olivier Soriani,David Bernard

    The identification of senolytics, compounds that eliminate senescent cells, is presently a key priority given their therapeutic promise in cancer and aging-associated diseases. Two recent papers by Triana-Martínez et al. and Guerrero et al. report the senolytic activity of cardiac glycosides (CGs) and their efficacy in these pathophysiological contexts.

  • Commercialization of Organoids.
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-01-22
    Deepak Choudhury,Aswathi Ashok,May Win Naing

    Organoids have been successfully exploited for drug screening, disease modeling, pathogenesis, and regenerative medicine. Herein, we discuss the progress achieved in the commercialization of organoids in the last few years. We further elaborate on the concept of organoid biobank and highlight ethical and regulatory issues surrounding organoid research and commercialization.

  • Glymphatic System Impairment in Alzheimer's Disease and Idiopathic Normal Pressure Hydrocephalus.
    Trends Mol. Med. (IF 11.028) Pub Date : 2020-01-18
    Benjamin C Reeves,Jason K Karimy,Adam J Kundishora,Humberto Mestre,H Mert Cerci,Charles Matouk,Seth L Alper,Iben Lundgaard,Maiken Nedergaard,Kristopher T Kahle

    Approximately 10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer's disease (AD) both exhibit sleep disturbances, build-up of brain metabolic wastes and amyloid-β (Aβ) plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte aquaporin-4 (AQP4). The glia-lymphatic

  • Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-12-17
    Amit Bar-Or,Michael P Pender,Rajiv Khanna,Lawrence Steinman,Hans-Peter Hartung,Tap Maniar,Ed Croze,Blake T Aftab,Gavin Giovannoni,Manher J Joshi

    New treatments for multiple sclerosis (MS) focused on B cells have created an atmosphere of excitement in the MS community. B cells are now known to play a major role in disease, demonstrated by the highly impactful effect of a B cell-depleting antibody on controlling MS. The idea that a virus may play a role in the development of MS has a long history and is supported mostly by studies demonstrating

  • Vitamins for the Gut Microbiome.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-12-17
    Robert E Steinert,Yuan-Kun Lee,Wilbert Sybesma

    A main target in microbiome research is the understanding and ability to safely and effectively modulate the microbiome to improve health. Hereto, we discuss the role of vitamins in relation to the gut microbiome and present a rationale for the modulation of gut microbial communities via selected systemic and colon-targeted vitamin administration.

  • Resolving Spliceosomal Malfunctions Advances RNA-Based Therapeutics.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-12-10
    Zhao Zhang,Shengli Li,Leng Han

    Spliceosomes comprise small nuclear (sn)RNAs and proteins. Through genome-wide analyses in large-scale tumor samples, recent studies by Shuai et al., Suzuki et al., and Inoue et al. have identified recurrent spliceosomal mutations that induced genome-wide splicing alterations of cancer-related genes to promote malignancy. These discoveries suggest novel RNA-based therapeutics in anticancer treatment

  • Missing Pieces to the Endocannabinoid Puzzle.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-12-07
    Mauro Maccarrone

    The most bioactive ingredient of cannabis (Cannabis sativa or indica) extracts, Δ9-tetrahydrocannabinol (THC), was identified in the 1960s as one of more than 110 phytocannabinoids. It activates receptors of chemically different endogenous ligands (endocannabinoids) that, unlike THC, are metabolized by several enzymes of the endocannabinoid system. Here, the complexity of the plant-derived and endogenous

  • Editing Cytoprotective Autophagy in Glioma: An Unfulfilled Potential for Therapy.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-29
    Ilya Ulasov,Jawad Fares,Petr Timashev,Maciej S Lesniak

    Glioblastoma (GBM) resistance to the standard of care is prompting scientists to develop better targeted therapeutic strategies. Autophagy is one of the many signaling mechanisms that regulate tumor regrowth. Despite the extensive in vitro and in vivo studies published, knowledge on autophagic modulation remains scarce. This hinders the development of novel treatment modalities that employ autophagic

  • CRISPR Diagnosis and Therapeutics with Single Base Pair Precision.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-29
    Seung Hwan Lee,Young-Ho Park,Yeung Bae Jin,Sun-Uk Kim,Junho K Hur

    Clustered regularly interspaced short palindromic repeats, or CRISPR, has been widely accepted as a versatile genome editing tool with significant potential for medical application. Reliable allele specificity is one of the most critical elements for successful application of this technology to develop high-precision therapeutics and diagnostics. CRISPR-based genome editing tools achieve high-fidelity

  • Microbe-MUC1 Crosstalk in Cancer-Associated Infections.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-18
    Mukulika Bose,Pinku Mukherjee

    Infection-associated cancers account for ∼20% of all malignancies. Understanding the molecular mechanisms underlying infection-associated malignancies may help in developing diagnostic biomarkers and preventative vaccines against malignancy. During infection, invading microbes interact with host mucins lining the glandular epithelial cells and trigger inflammation. MUC1 is a transmembrane mucin glycoprotein

  • Mitophagy and Neuroprotection.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-07-30
    Guofeng Lou,Konstantinos Palikaras,Sofie Lautrup,Morten Scheibye-Knudsen,Nektarios Tavernarakis,Evandro F Fang

    Neurodegenerative diseases are strongly age-related and currently cannot be cured, with a surge of patient numbers in the coming decades in view of the emerging worldwide ageing population, bringing healthcare and socioeconomic challenges. Effective therapies are urgently needed, and are dependent on new aetiological mechanisms. In neurons, efficient clearance of damaged mitochondria, through the highly

  • The Mitochondrion as an Emerging Therapeutic Target in Cancer.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-07-18
    Katherine G Roth,Isa Mambetsariev,Prakash Kulkarni,Ravi Salgia

    Mitochondria have emerged as important pharmacological targets because of their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis. Furthermore, mitochondria can engage in crosstalk with the tumor microenvironment, and signals from cancer-associated fibroblasts can impinge

  • Mitochondrial Regulation of Stem Cells in Bone Homeostasis.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-05-21
    Chen-Xi Zheng,Bing-Dong Sui,Xin-Yu Qiu,Cheng-Hu Hu,Yan Jin

    Mitochondria have emerged as key contributors to the organismal homeostasis, in which mitochondrial regulation of stem cells is becoming increasingly important. Originated from mesenchymal stem cell (MSC) and hematopoietic stem cell (HSC) lineage commitments and interactions, bone is a representative organ where the mitochondrial essentiality to stem cell function has most recently been discovered

  • Staying in Healthy Contact: How Peroxisomes Interact with Other Cell Organelles.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-11
    Yelena Sargsyan,Sven Thoms

    Peroxisomes share extensive metabolic connections with other cell organelles. Membrane contact sites (MCSs) establish and maintain such interactions, and they are vital for organelle positioning and motility. In the past few years peroxisome interactions and MCSs with other cellular organelles have been explored extensively, resulting in the identification of new MCSs, the tethering molecules involved

  • Crosstalk between Sertoli and Germ Cells in Male Fertility.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-11
    Siwen Wu,Ming Yan,Renshan Ge,C Yan Cheng

    Spermatogenesis is supported by intricate crosstalk between Sertoli cells and germ cells including spermatogonia, spermatocytes, haploid spermatids, and spermatozoa, which takes place in the epithelium of seminiferous tubules. Sertoli cells, also known as 'mother' or 'nurse' cells, provide nutrients, paracrine factors, cytokines, and other biomolecules to support germ cell development. Sertoli cells

  • Strengthening Causal Inference for Complex Disease Using Molecular Quantitative Trait Loci.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-09
    Sonja Neumeyer,Gibran Hemani,Eleftheria Zeggini

    Large genome-wide association studies (GWAS) have identified loci that are associated with complex traits and diseases, but index variants are often not causal and reside in non-coding regions of the genome. To gain a better understanding of the relevant biological mechanisms, intermediate traits such as gene expression and protein levels are increasingly being investigated because these are likely

  • Glucocorticoid Maturation of Fetal Cardiovascular Function.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-09
    Juanita K Jellyman,Andrew J W Fletcher,Abigail L Fowden,Dino A Giussani

    The last decade has seen rapid advances in the understanding of the central role of glucocorticoids in preparing the fetus for life after birth. However, relative to other organ systems, maturation by glucocorticoids of the fetal cardiovascular system has been ignored. Here, we review the effects of glucocorticoids on fetal basal cardiovascular function and on the fetal cardiovascular defense responses

  • Challenges and Opportunities for Translation of Therapies to Improve Cognition in Down Syndrome.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-07
    Sarah E Lee,Monica Duran-Martinez,Sabina Khantsis,Diana W Bianchi,Faycal Guedj

    While preclinical studies have reported improvement of behavioral deficits in the Ts65Dn mouse model of Down syndrome (DS), translation to human clinical trials to improve cognition in individuals with DS has had a poor success record. Timing of the intervention, choice of animal models, strategy for drug selection, and lack of translational endpoints between animals and humans contributed to prior

  • Visualizing Mitochondrial Form and Function within the Cell.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-06
    Brian Glancy

    The specific cellular role of mitochondria is influenced by the surrounding environment because effective mitochondrial function requires the delivery of inputs (e.g., oxygen) and export of products (e.g., signaling molecules) to and from other cellular components, respectively. Recent technological developments in mitochondrial imaging have led to a more precise and comprehensive understanding of

  • MCL1 as a Therapeutic Target in Parkinson's Disease?
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-06
    Edward J. Robinson, Sebastian Aguiar, Marten P. Smidt, Lars P. van der Heide

    Dopamine neurons in the substantia nigra (SN) pars compacta are selectively lost during the progression of Parkinson’s disease (PD). Recent work performed on the role of the Bcl2 family (highly specialized proteins which control cellular survival and death) in midbrain dopamine neurons has led to the identification of the Bcl2 factor Mcl1 as a weak link in the survival of these neurons. We hypothesize

  • Applications of Spherical Nucleic Acid Nanoparticles as Delivery Systems
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-06
    Ahad Mokhtarzadeh, Hassan Vahidnezhad, Leila Youssefian, Jafar Mosafer, Behzad Baradaran, Jouni Uitto

    Spherical nucleic acids (SNAs) are nanostructures consisting of highly oriented, dense layers of oligonucleotides arranged in a spherical 3D geometry. Owing to their unique properties and function, SNAs occupy a material space distinct from 'DNA nanotechnology' and DNA origami. Over the past two decades SNAs have revolutionized gene regulation, drug delivery, gene therapy, and molecular diagnostics

  • Tailoring mRNA Vaccine to Balance Innate/Adaptive Immune Response.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-05
    Sergio Linares-Fernández,Céline Lacroix,Jean-Yves Exposito,Bernard Verrier

    mRNA vaccine platforms present numerous advantages, such as versatility, rapid production, and induction of cellular and humoral responses. Moreover, mRNAs have inherent adjuvant properties due to their complex interaction with pattern recognition receptors (PRRs). This recognition can be either beneficial in activating antigen-presenting cells (APCs) or detrimental by indirectly blocking mRNA translation

  • Organotypic Neurovascular Models: Past Results and Future Directions.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-04
    Daniel A Balikov,Emma H Neal,Ethan S Lippmann

    The high failure rates of clinical trials in neurodegeneration, perhaps most apparent in recent high-profile failures of potential Alzheimer's disease therapies, have partially motivated the development of improved human cell-based models to bridge the gap between well-plate assays and preclinical efficacy studies in mice. Recently, cerebral organoids derived from stem cells have gained significant

  • Nrf2: Redox and Metabolic Regulator of Stem Cell State and Function.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-01
    Xiaozhen Dai,Xiaoqing Yan,Kupper A Wintergerst,Lu Cai,Bradley B Keller,Yi Tan

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is ubiquitously expressed in most eukaryotic cells and functions to induce a broad range of cellular defenses against exogenous and endogenous stresses, including oxidants, xenobiotics, and excessive nutrient/metabolite supply. Because the production and fate of stem cells are often modulated by cellular redox and metabolic homeostasis, important roles

  • The 3D Genome as a Target for Anticancer Therapy.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-10-31
    Omar L Kantidze,Katerina V Gurova,Vasily M Studitsky,Sergey V Razin

    The role of 3D genome organization in the precise regulation of gene expression is well established. Accordingly, the mechanistic connections between 3D genome alterations and disease development are becoming increasingly apparent. This opinion article provides a snapshot of our current understanding of the 3D genome alterations associated with cancers. We discuss potential connections of the 3D genome

  • Mitochondria - A Powerful Therapeutic Target.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-11-14
    Claudia Willmes

  • 更新日期:2019-11-01
  • WITHDRAWN: 2018 Editorial Board Top Ten.
    Trends Mol. Med. (IF 11.028) Pub Date : 2019-02-10
    Claudia Willmes

    This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

  • Katalin Susztak.
    Trends Mol. Med. (IF 11.028) Pub Date : 2018-07-08

  • NEMO Links Nuclear Factor-κB to Human Diseases: (Trends Mol Med. 23, 1138-1155; 2017).
    Trends Mol. Med. (IF 11.028) Pub Date : 2018-02-20
    Gunter Maubach,Ann-Christin Schmädicke,Michael Naumann

  • Finding the Roots: Molecularly Tracking Substance Addiction.
    Trends Mol. Med. (IF 11.028) Pub Date : 2018-02-06
    Catarina Sacristán

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