Treatment and Prevention of Neurocristopathies
Trends Mol Med. 2021 Feb 22:S1471-4914(21)00041-1. doi: 10.1016/j.molmed.2021.01.009. Online ahead of print.ABSTRACTNeurocristopathies form a heterogeneous group of rare diseases caused by abnormal development of neural crest cells. Heterogeneity of neurocristopathies directly relates to the nature of these migratory and multipotent cells, which generate dozens of specialized cell types throughout the body. Neurocristopathies are thus characterized by congenital malformations of tissues/organs that otherwise appear to have very little in common, such as the craniofacial skeleton and enteric nervous system. Treatment option...
Source: Trends in Molecular Medicine - February 25, 2021 Category: Molecular Biology Authors: Nicolas Pilon Source Type: research

Treatment and Prevention of Neurocristopathies
Trends Mol Med. 2021 Feb 22:S1471-4914(21)00041-1. doi: 10.1016/j.molmed.2021.01.009. Online ahead of print.ABSTRACTNeurocristopathies form a heterogeneous group of rare diseases caused by abnormal development of neural crest cells. Heterogeneity of neurocristopathies directly relates to the nature of these migratory and multipotent cells, which generate dozens of specialized cell types throughout the body. Neurocristopathies are thus characterized by congenital malformations of tissues/organs that otherwise appear to have very little in common, such as the craniofacial skeleton and enteric nervous system. Treatment option...
Source: Trends in Molecular Medicine - February 25, 2021 Category: Molecular Biology Authors: Nicolas Pilon Source Type: research

Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies: (Trends in Molecular Medicine, 26:3 p:296-310, 2020)
Trends Mol Med. 2021 Feb 17:S1471-4914(21)00035-6. doi: 10.1016/j.molmed.2021.01.004. Online ahead of print.NO ABSTRACTPMID:33608230 | DOI:10.1016/j.molmed.2021.01.004 (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - February 20, 2021 Category: Molecular Biology Authors: Amit Bar-Or Michael P Pender Rajiv Khanna Lawrence Steinman Hans-Peter Hartung Tap Maniar Ed Croze Blake T Aftab Gavin Giovannoni Manher A Joshi Source Type: research

Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies: (Trends in Molecular Medicine, 26:3 p:296-310, 2020)
Trends Mol Med. 2021 Feb 17:S1471-4914(21)00035-6. doi: 10.1016/j.molmed.2021.01.004. Online ahead of print.NO ABSTRACTPMID:33608230 | DOI:10.1016/j.molmed.2021.01.004 (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - February 20, 2021 Category: Molecular Biology Authors: Amit Bar-Or Michael P Pender Rajiv Khanna Lawrence Steinman Hans-Peter Hartung Tap Maniar Ed Croze Blake T Aftab Gavin Giovannoni Manher A Joshi Source Type: research

Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies: (Trends in Molecular Medicine, 26:3 p:296-310, 2020).
PMID: 33608230 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - February 17, 2021 Category: Molecular Biology Authors: Bar-Or A, Pender MP, Khanna R, Steinman L, Hartung HP, Maniar T, Croze E, Aftab BT, Giovannoni G, Joshi MA Tags: Trends Mol Med Source Type: research

Stories in Molecular Medicine.
Authors: PMID: 33568327 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - February 8, 2021 Category: Molecular Biology Tags: Trends Mol Med Source Type: research

Ubiquitous Chromatin Modifiers in Congenital Retinal Diseases: Implications for Disease Modeling and Regenerative Medicine.
Abstract Retinal congenital malformations known as microphthalmia, anophthalmia, and coloboma (MAC) are associated with alterations in genes encoding epigenetic proteins that modify chromatin. We review newly discovered functions of such chromatin modifiers in retinal development and discuss the role of epigenetics in MAC in humans and animal models. Further, we highlight how advances in epigenomic technologies provide foundational and regenerative medicine-related insights into blinding disorders. Combining knowledge of epigenetics and pluripotent stem cells (PSCs) is a promising avenue because epigenetic factors...
Source: Trends in Molecular Medicine - February 8, 2021 Category: Molecular Biology Authors: Basinski BW, Balikov DA, Aksu M, Li Q, Rao RC Tags: Trends Mol Med Source Type: research

Data-Driven Modeling of Pregnancy-Related Complications.
Abstract A healthy pregnancy depends on complex interrelated biological adaptations involving placentation, maternal immune responses, and hormonal homeostasis. Recent advances in high-throughput technologies have provided access to multiomics biological data that, combined with clinical and social data, can provide a deeper understanding of normal and abnormal pregnancies. Integration of these heterogeneous datasets using state-of-the-art machine-learning methods can enable the prediction of short- and long-term health trajectories for a mother and offspring and the development of treatments to prevent or minimiz...
Source: Trends in Molecular Medicine - February 8, 2021 Category: Molecular Biology Authors: Espinosa C, Becker M, Marić I, Wong RJ, Shaw GM, Gaudilliere B, Aghaeepour N, Stevenson DK, Prematurity Research Center Tags: Trends Mol Med Source Type: research

Breakthroughs and Bottlenecks in Microbiome Research.
Abstract Over the past 15 years, the research community has witnessed unprecedented progress in microbiome research. We review this increasing knowledge and first attempts of its clinical application, and also limitations and challenges faced by the research community, in mechanistically understanding host-microbiome interactions and integrating these insights into clinical practice. PMID: 33563544 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - February 6, 2021 Category: Molecular Biology Authors: Liwinski T, Leshem A, Elinav E Tags: Trends Mol Med Source Type: research

Delaying Reproductive Aging by Ovarian Tissue Cryopreservation and Transplantation: Is it Prime Time?
Abstract Ovarian tissue cryopreservation and autotransplantation can restore ovarian endocrine function and fertility and recently were changed from experimental to fertility preservation procedures for medical indications by the American Society of Reproductive Medicine. Such advances have resulted in discussions around the utility of ovarian cryopreservation in healthy women to preserve fertility and delay menopause or as a hormone replacement approach. Such 'elective' use of ovarian tissue cryopreservation requires a risk-benefit assessment. Here, we review evidence for and against the utility of ovarian tissue...
Source: Trends in Molecular Medicine - February 3, 2021 Category: Molecular Biology Authors: Oktay KH, Marin L, Petrikovsky B, Terrani M, Babayev SN Tags: Trends Mol Med Source Type: research

Stories in Molecular Medicine: February 2021.
Authors: PMID: 33513344 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - January 31, 2021 Category: Molecular Biology Tags: Trends Mol Med Source Type: research

Liquid Biopsy of Methylation Biomarkers in Cell-Free DNA.
Abstract Liquid biopsies, in particular, analysis of cell-free DNA (cfDNA), have emerged as a promising noninvasive diagnostic approach in oncology. Abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. Systemic analysis of cfDNA methylation profiles is being developed for cancer early detection, monitoring for minimal residual disease (MRD), predicting treatment response and prognosis, and tracing the tissue origin. This review highlights the advantages and disadvantages of ctDNA profiling for noninvasive diagnosis of early-stag...
Source: Trends in Molecular Medicine - January 23, 2021 Category: Molecular Biology Authors: Luo H, Wei W, Ye Z, Zheng J, Xu RH Tags: Trends Mol Med Source Type: research

Mining Helminths for Novel Therapeutics.
Abstract Helminths are an emerging source of therapeutics for dysregulated inflammatory diseases. Excretory/secretory (ES) molecules, released during infection, are responsible for many of these immunomodulatory effects and are likely to have evolved as a means for parasite survival in the host. While the mechanisms of action of these molecules have not been fully defined, evidence demonstrates that they target various pathways in the immune response, ranging from initiation to effector cell modulation. These molecules are applied in controlling specific effector mechanisms of type 1 and type 2 immune responses. R...
Source: Trends in Molecular Medicine - January 23, 2021 Category: Molecular Biology Authors: Lothstein KE, Gause WC Tags: Trends Mol Med Source Type: research

Expanding the Toolbox and Targets for Gene Editing.
Abstract Genome editing holds great promise for treating a range of human genetic diseases. While emerging clustered regularly interspaced short-palindromic repeats (CRISPR) technologies allow editing of the nuclear genome, it is still not possible to precisely manipulate mitochondrial DNA (mtDNA). Here, we summarize past developments and recent advances in nuclear and mitochondrial genome editing. PMID: 33487569 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - January 21, 2021 Category: Molecular Biology Authors: Dan J, Memczak S, Izpisua Belmonte JC Tags: Trends Mol Med Source Type: research

Preimplantation Genetic Testing for Aneuploidy - a Castle Built on Sand.
Abstract Preimplantation genetic testing for aneuploidy (PGT-A) has become a routine add-on for in vitro fertilization (IVF) to determine whether human embryos are to be clinically utilized or disposed of. Studies claiming IVF outcome improvements following PGT-A, however, used highly selected patient populations or inappropriate statistical methodologies. PGT-A was never clinically validated in its ability to define a human embryo as chromosomal normal, mosaic, or aneuploid, nor certified by a regulatory body, or an authoritative professional organization. Because of a high false-positive rate, PGT-A, actually re...
Source: Trends in Molecular Medicine - January 11, 2021 Category: Molecular Biology Authors: Gleicher N, Patrizio P, Brivanlou A Tags: Trends Mol Med Source Type: research

Multivalent Probes in Molecular Imaging: Reality or Future?
PH Abstract The rapidly developing field of molecular medical imaging focuses on specific visualization of (patho)physiological processes through the application of imaging agents (IAs) in multiple clinical modalities. Although our understanding of the principles underlying efficient IAs design has increased tremendously, many IAs still show poor in vivo imaging performance because of low binding affinity and/or specificity. These limitations can be addressed by taking advantage of multivalency, in which multiple copies of a ligand are employed to strengthen the interaction. We critically address specific challen...
Source: Trends in Molecular Medicine - January 9, 2021 Category: Molecular Biology Authors: Böhmer VI, Szymanski W, Feringa BL, Elsinga PH Tags: Trends Mol Med Source Type: research

T Cells as Guardians of Pain Resolution.
Abstract Despite successful research efforts aimed at understanding pain mechanisms, there is still no adequate treatment for many patients suffering from chronic pain. The contribution of neuroinflammation to chronic pain is widely acknowledged. Here, we summarize findings indicating that T cells play a key role in the suppression of pain. An active contribution of the immune system to resolution of pain may explain why immunosuppressive drugs are often not sufficient to control pain. This would also imply that dysregulation of certain immune functions promote transition to chronic pain. Conversely, stimulating t...
Source: Trends in Molecular Medicine - January 8, 2021 Category: Molecular Biology Authors: Kavelaars A, Heijnen CJ Tags: Trends Mol Med Source Type: research

Strategies to Identify Genetic Variants Causing Infertility.
Abstract Genetic causes are thought to underlie about half of infertility cases, but understanding the genetic bases has been a major challenge. Modern genomics tools allow more sophisticated exploration of genetic causes of infertility through population, family-based, and individual studies. Nevertheless, potential therapies based on genetic diagnostics will be limited until there is certainty regarding the causality of genetic variants identified in an individual. Genome modulation and editing technologies have revolutionized our ability to functionally test such variants, and also provide a potential means for...
Source: Trends in Molecular Medicine - January 8, 2021 Category: Molecular Biology Authors: Ding X, Schimenti JC Tags: Trends Mol Med Source Type: research

Avoiding a Sticky Situation: Bypassing the Mucus Barrier for Improved Local Drug Delivery.
Abstract The efficacy of drugs administered by traditional routes is limited by numerous biological barriers that preclude reaching the intended site of action. Further, full body systemic exposure leads to dose-limiting, off-target side effects. Topical formulations may provide more efficacious drug and nucleic acid delivery for diseases and conditions affecting mucosal tissues, but the mucus protecting our epithelial surfaces is a formidable barrier. Here, we describe recent advances in mucus-penetrating approaches for drug and nucleic acid delivery to the ocular surface, the female reproductive tract, the gastr...
Source: Trends in Molecular Medicine - January 4, 2021 Category: Molecular Biology Authors: Zierden HC, Josyula A, Shapiro RL, Hsueh HT, Hanes J, Ensign LM Tags: Trends Mol Med Source Type: research

Cellular Models and High-Throughput Screening for Genetic Causality of Intellectual Disability.
Abstract Intellectual disabilities (ID) are a type of neurodevelopmental disorder (NDD). They can have a genetic cause, including an emerging class of ID centring around Rho GTPases, such as Ras-related C3 botulinum toxin substrate 1 (RAC1). Guidelines for establishing genetic causality include the use of cellular models, which often have morphological aberrations, a long-standing hallmark of ID. Disease cellular models can facilitate high-throughput screening (HTS) of chemical or genetic perturbations, which can provide translatable biological insight. Here, we discuss a class of IDs centring around RAC1. We revi...
Source: Trends in Molecular Medicine - January 2, 2021 Category: Molecular Biology Authors: Fell CW, Nagy V Tags: Trends Mol Med Source Type: research

Post-Transcriptional Regulation in Skeletal Muscle Development, Repair, and Disease.
Abstract Skeletal muscle formation is a complex process that requires tight spatiotemporal control of key myogenic factors. Emerging evidence suggests that RNA processing is crucial for the regulation of these factors, and that multiple post-transcriptional regulatory pathways work dependently and independently of one another to enable precise control of transcripts throughout muscle development and repair. Moreover, disruption of these pathways is implicated in neuromuscular disease, and the recent development of RNA-mediated therapies shows enormous promise in the treatment of these disorders. We discuss the ove...
Source: Trends in Molecular Medicine - December 28, 2020 Category: Molecular Biology Authors: Weskamp K, Olwin BB, Parker R Tags: Trends Mol Med Source Type: research

A Rare Kidney Disease To Cure Them All? Towards Mechanism-Based Therapies for Proteinopathies.
Abstract Autosomal dominant tubulointerstitial kidney diseases (ADTKDs) are a group of rare genetic diseases that lead to kidney failure. Mutations in the MUC1 gene cause ADTKD-MUC1 (MUC1 kidney disease, MKD), a disorder with no available therapies. Recent studies have identified the molecular and cellular mechanisms that drive MKD disease pathogenesis. Armed with patient-derived cell lines and pluripotent stem cell (iPSC)-derived kidney organoids, it was found that MKD is a toxic proteinopathy caused by the intracellular accumulation of misfolded MUC1 protein in the early secretory pathway. We discuss the advanta...
Source: Trends in Molecular Medicine - December 16, 2020 Category: Molecular Biology Authors: Dvela-Levitt M, Shaw JL, Greka A Tags: Trends Mol Med Source Type: research

The Need for Research-Grade Systems Modeling Technologies for Life Science Education.
Abstract The coronavirus disease 2019 (COVID-19) pandemic not only challenged deeply-rooted daily patterns but also put a spotlight on the role of computational modeling in science and society. Amid the impromptu upheaval of in-person education across the world, this article aims to articulate the need to train students in computational and systems biology using research-grade technologies. PMID: 33334676 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - December 15, 2020 Category: Molecular Biology Authors: Helikar T Tags: Trends Mol Med Source Type: research

Permeability of the Endothelial Barrier: Identifying and Reconciling Controversies.
Abstract Leakage from blood vessels into tissues is governed by mechanisms that control endothelial barrier function to maintain homeostasis. Dysregulated endothelial permeability contributes to many conditions and can influence disease morbidity and treatment. Diverse approaches used to study endothelial permeability have yielded a wealth of valuable insights. Yet, ongoing questions, technical challenges, and unresolved controversies relating to the mechanisms and relative contributions of barrier regulation, transendothelial sieving, and transport of fluid, solutes, and particulates complicate interpretations in...
Source: Trends in Molecular Medicine - December 10, 2020 Category: Molecular Biology Authors: Claesson-Welsh L, Dejana E, McDonald DM Tags: Trends Mol Med Source Type: research

Fertility Preservation: The Challenge of Freezing and Transplanting Ovarian Tissue.
Abstract Cancer treatments are increasingly effective, but can result in iatrogenic premature ovarian insufficiency. Ovarian tissue cryopreservation is the only option available to preserve fertility in prepubertal girls and young women who require immediate chemotherapy. Ovarian tissue transplantation has been shown to restore hormonal cycles and fertility, but a large proportion of the follicle reserve is lost as a consequence of exposure to hypoxia. Another crucial concern is the risk of reimplanting malignant cells together with the grafted tissue. In this review, the authors advance some challenging propositi...
Source: Trends in Molecular Medicine - December 9, 2020 Category: Molecular Biology Authors: Dolmans MM, Donnez J, Cacciottola L Tags: Trends Mol Med Source Type: research

Ecosystem Barriers to Innovation Adoption in Clinical Practice.
Abstract Despite increasing ability to understand and correct molecular derangements in disease, genomics and novel phenotypic assays are unevenly deployed in clinical practice. This has hampered translational research and our ability to identify clinically actionable subtypes of disease. Historic examples illustrate how the perspectives of stakeholders across the healthcare ecosystem can influence adoption of innovations in healthcare. Consideration of these factors, from discovery to implementation, can accelerate adoption of new molecular and digital phenotypes in a 'learning' healthcare ecosystem. PMID: 3...
Source: Trends in Molecular Medicine - December 5, 2020 Category: Molecular Biology Authors: MacRae CA, Deo RC, Shaw SY Tags: Trends Mol Med Source Type: research

Stories in Molecular Medicine.
Authors: PMID: 33272773 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - November 30, 2020 Category: Molecular Biology Tags: Trends Mol Med Source Type: research

Extracellular Vesicles and Biomaterial Design: New Therapies for Cardiac Repair.
te; P Abstract There is increasing evidence that extracellular vesicles (EVs) mediate the paracrine effects of stem cells. Although EVs have several attractive characteristics, they also raise issues related to delivery. For patients with cardiac disease that require a surgical procedure, direct intramyocardial (IM) administration of EVs is straightforward but its efficacy may be limited by fast wash-out, hence the interest of incorporating EVs into a controlled release polymer to optimize their residence time. For patients without surgical indication, the intravenous (IV) route is attractive because of its lack o...
Source: Trends in Molecular Medicine - November 17, 2020 Category: Molecular Biology Authors: Pezzana C, Agnely F, Bochot A, Siepmann J, Menasché P Tags: Trends Mol Med Source Type: research

PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies.
Abstract Immune checkpoints negatively regulate immune cell responses. Programmed cell death protein 1:programmed death ligand 1 (PD-1:PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4):B7-1 are among the most important immune checkpoint pathways, and are key targets for immunotherapies that seek to modulate the balance between stimulatory and inhibitory signals to lead to favorable therapeutic outcomes. The current dogma of these two immune checkpoint pathways has regarded them as independent with no interactions. However, the newly characterized PD-L1:B7-1 ligand-ligand cis-interaction and its abili...
Source: Trends in Molecular Medicine - November 13, 2020 Category: Molecular Biology Authors: Nishimura CD, Pulanco MC, Cui W, Lu L, Zang X Tags: Trends Mol Med Source Type: research

Deciphering the Identity of Renin Cells in Health and Disease.
Abstract Hypotension and changes in fluid-electrolyte balance pose immediate threats to survival. Juxtaglomerular cells respond to such threats by increasing the synthesis and secretion of renin. In addition, smooth muscle cells (SMCs) along the renal arterioles transform into renin cells until homeostasis has been regained. However, chronic unrelenting stimulation of renin cells leads to severe kidney damage. Here, we discuss the origin, distribution, function, and plasticity of renin cells within the kidney and immune compartments and the consequences of distorting the renin program. Understanding how chronic st...
Source: Trends in Molecular Medicine - November 5, 2020 Category: Molecular Biology Authors: Guessoum O, de Goes Martini A, Sequeira-Lopez MLS, Gomez RA Tags: Trends Mol Med Source Type: research

Intercellular Communication in the Heart: Therapeutic Opportunities for Cardiac Ischemia.
Abstract The maintenance of tissue, organ, and organism homeostasis relies on an intricate network of players and mechanisms that assist in the different forms of cell-cell communication. Myocardial infarction, following heart ischemia and reperfusion, is associated with profound changes in key processes of intercellular communication, involving gap junctions, extracellular vesicles, and tunneling nanotubes, some of which have been implicated in communication defects associated with cardiac injury, namely arrhythmogenesis and progression into heart failure. Therefore, intercellular communication players have emerg...
Source: Trends in Molecular Medicine - October 30, 2020 Category: Molecular Biology Authors: Martins-Marques T, Hausenloy DJ, Sluijter JPG, Leybaert L, Girao H Tags: Trends Mol Med Source Type: research

Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease.
Abstract Neurodegenerative diseases (NDDs) are a heterogeneous group of diseases that are characterized by the progressive loss of neurons leading to motor, sensory, and/or cognitive defects. Currently, NDDs are not curable and treatment focuses on alleviating symptoms and halting disease progression. Phenotypic heterogeneity between individual NDD patients, lack of robust biomarkers, the limited translational potential of experimental models, and other factors have hampered drug development for the treatment of NDDs. This review summarizes and discusses the use of induced pluripotent stem cell (iPSC) approaches f...
Source: Trends in Molecular Medicine - October 26, 2020 Category: Molecular Biology Authors: Pasteuning-Vuhman S, de Jongh R, Timmers A, Pasterkamp RJ Tags: Trends Mol Med Source Type: research

Extinguishing the Embers: Targeting AML Metabolism.
Abstract Acute myeloid leukemia (AML) is a cancer derived from the myeloid lineage of blood cells, characterized by overproduction of leukemic blasts. Although therapeutic improvements have made a significant impact on the outcomes of patients with AML, survival rates remain low due to a high incidence of relapse. Similar to how wildfires can reignite from hidden embers not extinguished from an initial round of firefighting, leukemic stem cells (LSCs) are the embers remaining after completion of traditional chemotherapeutic treatments. LSCs exhibit a unique metabolic profile and contain metabolically distinct subp...
Source: Trends in Molecular Medicine - October 26, 2020 Category: Molecular Biology Authors: Culp-Hill R, D'Alessandro A, Pietras EM Tags: Trends Mol Med Source Type: research

Influenza A Viruses: Understanding Human Host Determinants.
Abstract Previous influenza A virus (IAV) pandemics have invariably been caused by the introduction of an emergent IAV strain from an animal host into a human population with no or only little pre-existing immunity to the novel strain. Although zoonotic spillover of IAVs into humans can be associated with severe disease and a high fatality rate, these strains are typically poorly adapted to humans and are unable to establish sustained transmission between humans. Given the presumably very high degree of exposure to animal populations with endemic IAV, the number of pandemics remains surprisingly low. In this revie...
Source: Trends in Molecular Medicine - October 20, 2020 Category: Molecular Biology Authors: Ciminski K, Chase GP, Beer M, Schwemmle M Tags: Trends Mol Med Source Type: research

Therapeutic Approaches in Facioscapulohumeral Muscular Dystrophy.
Abstract Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common types of muscular dystrophy, affecting roughly one in 8000 individuals. The complex underlying genetics and poor mechanistic understanding has caused a bottleneck in therapeutic development. Until the discovery of DUX4 and its causal role in FSHD, most trials were untargeted with limited results. Emerging approaches can learn from these early trials to increase their chance of success. Here, we explore the evolution of FSHD clinical trials from nonspecific anabolic or anti-inflammatory/oxidant strategies to cutting-edge molecular ther...
Source: Trends in Molecular Medicine - October 19, 2020 Category: Molecular Biology Authors: Cohen J, DeSimone A, Lek M, Lek A Tags: Trends Mol Med Source Type: research

DNA Damage Repair Deficiency and Synthetic Lethality for Cancer Treatment.
PMID: 33077400 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - October 16, 2020 Category: Molecular Biology Authors: Burdak-Rothkamm S, Rothkamm K Tags: Trends Mol Med Source Type: research

Journey to the Center of the Cell: Tracing the Path of AAV Transduction.
Abstract As adeno-associated virus (AAV)-based gene therapies are being increasingly approved for use in humans, it is important that we understand vector-host interactions in detail. With the advances in genome-wide genetic screening tools, a clear picture of AAV-host interactions is beginning to emerge. Understanding these interactions can provide insights into the viral life cycle. Accordingly, novel strategies to circumvent the current limitations of AAV-based vectors may be explored. Here, we summarize our current understanding of the various stages in the journey of the vector from the cell surface to the nu...
Source: Trends in Molecular Medicine - October 15, 2020 Category: Molecular Biology Authors: Dhungel BP, Bailey CG, Rasko JEJ Tags: Trends Mol Med Source Type: research

Predicting and Overcoming Taxane Chemoresistance.
Abstract Taxanes are microtubule-targeting drugs used as cytotoxic chemotherapy to treat most solid tumors. The development of resistance to taxanes is a major cause of therapeutic failure and overcoming chemoresistance remains an important challenge to improve patient's outcome. Extensive efforts have been made recently to identify predictive biomarkers to select populations of patients who will benefit from taxane-based chemotherapy and avoid inefficient treatment of patients with innate resistance. This, together with the discovery of new mechanisms of resistance that include metabolic reprogramming and dialogu...
Source: Trends in Molecular Medicine - October 9, 2020 Category: Molecular Biology Authors: Rodrigues-Ferreira S, Moindjie H, Haykal MM, Nahmias C Tags: Trends Mol Med Source Type: research

Leveraging Heterogeneity in Systemic Lupus Erythematosus for New Therapies.
Abstract Systemic lupus erythematosus (SLE) is a multisystem, chronic autoimmune disease where treatment varies by patient and disease activity. Strong preclinical results and clinical correlates have motivated development of many drugs, but many of these have failed to achieve efficacy in clinical trials. FDA approval of belimumab in 2011 was the first successful SLE drug in nearly six decades. In this article, we review insights into the molecular and clinical heterogeneity of SLE from transcriptomics studies and detail their potential impact on drug development and clinical practices. We critically examine the ...
Source: Trends in Molecular Medicine - October 9, 2020 Category: Molecular Biology Authors: Allen ME, Rus V, Szeto GL Tags: Trends Mol Med Source Type: research

ER α in the Control of Mitochondrial Function and Metabolic Health.
ERα in the Control of Mitochondrial Function and Metabolic Health. Trends Mol Med. 2020 Oct 02;: Authors: Hevener AL, Ribas V, Moore TM, Zhou Z Abstract Decrements in metabolic health elevate disease risk, including type 2 diabetes, heart disease, and certain cancers. Thus, treatment strategies to combat metabolic dysfunction are needed. Reduced ESR1 (estrogen receptor, ERα) expression is observed in muscle from women, men, and animals presenting clinical features of the metabolic syndrome. Human studies of natural expression of ESR1 in metabolic tissues show that muscle expression of ESR1...
Source: Trends in Molecular Medicine - October 1, 2020 Category: Molecular Biology Authors: Hevener AL, Ribas V, Moore TM, Zhou Z Tags: Trends Mol Med Source Type: research

Resilience to Stress and Resilience to Pain: Lessons from Molecular Neurobiology and Genetics.
Abstract What biological factors account for resilience to pain or to behavioral stress? Here, we discuss examples of cellular and molecular mechanisms within disparate parts of the nervous system as contributors to such resilience. In some especially well-studied humans, it is possible to identify particular neuronal cell types in the peripheral nervous system (PNS) and pinpoint specific genes that are major contributors to pain resilience. We also discuss more complex factors that operate within the central nervous system (CNS) to confer resilience to behavioral stress. We propose that genetic and neurobiologica...
Source: Trends in Molecular Medicine - September 27, 2020 Category: Molecular Biology Authors: Nestler EJ, Waxman SG Tags: Trends Mol Med Source Type: research

Targeting Ferroptosis: New Hope for As-Yet-Incurable Diseases.
Abstract Attaining control over life and death decisions facilitates the identification of new therapeutic strategies for diseases affected by early cell loss or resistance to cell death. In this context, ferroptosis, a prevailing form of non-apoptotic cell death marked by the iron-dependent oxidative destruction of lipid bilayers and metabolic aberrations, has attracted overwhelming interest among basic researchers and clinicians due to its relevance for a number of degenerative diseases, such as neurodegeneration, ischemia/reperfusion injury (IRI), and organ failure, as well as therapy-resistant tumors. As the f...
Source: Trends in Molecular Medicine - September 17, 2020 Category: Molecular Biology Authors: Conrad M, Lorenz SM, Proneth B Tags: Trends Mol Med Source Type: research

Therapeutic Opportunities for Repair GPCRs during Intestinal Mucosal Wound Healing.
Abstract G protein-coupled receptors (GPCRs) are crucial for establishing the resolution phase following an intestinal inflammatory episode. Because current treatments for intestinal inflammation have a high percentage of failure and lead to immunosuppression, repair GPCRs have promising therapeutic potential because they trigger resolution pathways without compromising the immune response. PMID: 32958405 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - September 17, 2020 Category: Molecular Biology Authors: Quiros M Tags: Trends Mol Med Source Type: research

Mitochondria as Therapeutic Targets in Transplantation.
Abstract Advances in surgical procedures, technology, and immune suppression have transformed organ transplantation. However, the metabolic changes that occur during organ retrieval, storage, and implantation have been relatively neglected since the developments many decades ago of cold storage organ preservation solutions. In this review we discuss how the metabolic changes that occur within the organ during transplantation, particularly those associated with mitochondria, may contribute to the outcome. We show how a better understanding of these processes can lead to changes in surgical practice and the developm...
Source: Trends in Molecular Medicine - September 16, 2020 Category: Molecular Biology Authors: Saeb-Parsy K, Martin JL, Summers DM, Watson CJE, Krieg T, Murphy MP Tags: Trends Mol Med Source Type: research

Pro-cathepsin D, Prosaposin, and Progranulin: Lysosomal Networks in Parkinsonism.
Abstract Mutations in GBA1, the gene encoding the lysosomal hydrolase glucocerebrosidase (GCase), are a risk factor for parkinsonism. Pursuing the potential mechanisms underlying this risk in aging neurons, we propose a new network uniting three major lysosomal proteins: (i) cathepsin D (CTSD), which plays a major role in α-synuclein (SNCA) degradation and prosaposin (PSAP) cleavage; (ii) PSAP, essential for GCase activation and progranulin (PGRN) transport; and (iii) PGRN, impacting lysosomal biogenesis, PSAP trafficking, and CTSD maturation. We hypothesize that alterations to this network and associated re...
Source: Trends in Molecular Medicine - September 14, 2020 Category: Molecular Biology Authors: Tayebi N, Lopez G, Do J, Sidransky E Tags: Trends Mol Med Source Type: research

Neuronal Reprogramming for Brain Repair: Challenges and Perspectives.
z M Abstract Brain injuries and neurodegenerative diseases elicit neuronal loss that persists because the adult mammalian brain lacks robust regenerative abilities. Direct reprogramming of local glial cells into neurons is a promising strategy for neuronal replacement in vivo. We discuss recent advances and future challenges in this approach to brain repair. PMID: 32943322 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - September 13, 2020 Category: Molecular Biology Authors: Bocchi R, Götz M Tags: Trends Mol Med Source Type: research

Blocking CTGF-Mediated Tumor-Stroma Interplay in Pancreatic Cancer.
Abstract As the major feature of pancreatic ductal adenocarcinoma (PDAC), desmoplastic stroma poses a significant obstacle for treatment. Recent studies revealed that connective tissue growth factor (CTGF) aggravates the fibrotic environment and drives cancer initiation and progression, thus suggesting CTGF as a novel target for PDAC treatment. PMID: 32928643 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - September 10, 2020 Category: Molecular Biology Authors: Shen YW, Zhou YD, Luan X, Zhang WD Tags: Trends Mol Med Source Type: research

Huntington's Disease: Les Jeux Sont Faits?
Abstract In a meticulous study, Humbert, Durr, and colleagues showed evidence for aberrant neurodevelopment in both Huntington's disease (HD) and mouse models of HD. We consider the implications of prenatal pathological changes for the onset and progression of HD and their relatedness to current therapeutic plans. PMID: 32893090 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - September 3, 2020 Category: Molecular Biology Authors: Pfister EL, Aronin N Tags: Trends Mol Med Source Type: research

Celebrating Molecular Medicine.
PMID: 32857967 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - August 30, 2020 Category: Molecular Biology Authors: Willmes CG Tags: Trends Mol Med Source Type: research

T Lymphocytes Cash Their Value in Clinical Medicine.
Abstract Empowering the ability of cytotoxic T cells to kill tumor cells or the reframing of their receptor to eliminate cancer cells has revolutionized cancer treatment. Simultaneously, the empowering of regulatory subsets has met success in mitigating autoimmune diseases. T cells, the major first responders of the immune system, are produced in the thymus, an organ that serves as their 'training camp'. On their exit to the periphery, T cells are effector cells that control infections or regulatory cells, which limit excessive responses. PMID: 32857968 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - August 30, 2020 Category: Molecular Biology Authors: Tsokos GC, Terhorst C Tags: Trends Mol Med Source Type: research