Epstein-Barr virus infection in the development of neurological disorders
Publication date: Available online 19 February 2020Source: Drug Discovery Today: Disease ModelsAuthor(s): Samantha S. Soldan, Paul M. LiebermanEpstein-Barr Virus (EBV) is a ubiquitous human herpesvirus that contributes to the etiology of diverse human cancers and auto-immune diseases. EBV establishes a relatively benign, long-term latent infection in over 90 percent of the adult population. Yet, it also increases risk for certain cancers and auto-immune disorders depending on complex viral, host, and environmental factors that are only partly understood. EBV latent infection is found predominantly in memory B cells, but th...
Source: Drug Discovery Today: Disease Models - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Models of rare diseases
Publication date: Available online 14 February 2020Source: Drug Discovery Today: Disease ModelsAuthor(s): Daniela Braconi, Annalisa Santucci (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - February 15, 2020 Category: Drugs & Pharmacology Source Type: research

Cell and tissue models of alkaptonuria
Publication date: Available online 25 January 2020Source: Drug Discovery Today: Disease ModelsAuthor(s): Daniela Braconi, Lia Millucci, Ottavia Spiga, Annalisa SantucciAlkaptonuria (AKU) is a rare metabolic disease of historical and medical interest. Despite the identification of gene and protein defects leading to the accumulation of homogentisic acid (HGA), little is known on how HGA is transformed into an ochronotic pigment (the hallmark of the disease) leading to a range of clinical manifestations. Major obstacles in tackling the pathological features of AKU are the rarity of biological samples, the invasiveness of sam...
Source: Drug Discovery Today: Disease Models - January 25, 2020 Category: Drugs & Pharmacology Source Type: research

The complexity of Rett syndrome models: Primary fibroblasts as a disease-in-a-dish reliable approach
Publication date: Available online 19 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Valeria Cordone, Alessandra Pecorelli, Fernanda Amicarelli, Joussef Hayek, Giuseppe ValacchiRett syndrome (RTT) is a progressive neurodevelopmental disease, which affects almost exclusively the female gender (prevalence of about 1:10,000). RTT symptoms are usually characterized by loss of purposeful hand skills, mental retardation and motor impairment, resulting in a plethora of other systemic co-morbidities. Mutations in the methyl-CpG binding protein 2 gene (MECP2) are the main genetic cause of the disorder, however ...
Source: Drug Discovery Today: Disease Models - December 21, 2019 Category: Drugs & Pharmacology Source Type: research

In vitro models of HIV-1 infection of the central nervous system
Publication date: Available online 20 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Celeste Faia, Karlie Plaisance-Bonstaff, Francesca PeruzziNeurocognitive disorders associated with HIV-1 infection affect more than half of persons living with HIV (PLWH) under retroviral therapy. Understanding the molecular mechanisms and the complex cellular network communication underlying neurological dysfunction is critical for the development of an effective therapy. As with other neurological disorders, challenges to studying HIV infection of the brain include limited access to clinical samples and proper reprod...
Source: Drug Discovery Today: Disease Models - December 21, 2019 Category: Drugs & Pharmacology Source Type: research

Do herpesviruses play a role in Alzheimer’s disease pathogenesis?
Publication date: Available online 18 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Mary Alice Allnutt, Steven JacobsonRecent studies have brought renewed interest to the hypothesis that infection plays a role in the pathogenesis of Alzheimer’s disease (AD). In particular, herpesviruses such as herpes simplex virus-1 (HSV-1) and human herpesvirus-6 (HHV-6) have had an extensive history of association with AD. The interplay between viral infection and a variety of neurological diseases has long been an area of interest but proving causality has been elusive. Two recent studies, Readhead et al. (2...
Source: Drug Discovery Today: Disease Models - December 18, 2019 Category: Drugs & Pharmacology Source Type: research

Disease models in cerebral cavernous malformations
Publication date: Available online 9 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Angela J. Glading, Federica Finetti, Lorenza TrabalziniCerebral cavernous malformation (CCM) is a rare disease of genetic origin characterized by dilated and leaky capillaries occurring mainly in the central nervous system. CCM can arise sporadically or may be inherited as an autosomal dominant condition with incomplete penetrance and variable clinical expressivity. The sporadic form accounts for up to 80% of cases, whereas the familial form accounts for at least 20% of cases. Genetic studies have identified three genes...
Source: Drug Discovery Today: Disease Models - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Chediak-Higashi syndrome: A review of the past, present, and future
Publication date: Available online 9 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Prashant Sharma, Elena-Raluca Nicoli, Jenny Serra-Vinardell, Marie Morimoto, Camilo Toro, May Christine V. Malicdan, Wendy J. IntroneSince the initial description of Chediak-Higashi syndrome (CHS), over 75 years ago, several studies have been conducted to underscore the role of the lysosomal trafficking regulator (LYST) gene in the pathogenesis of disease. CHS is a rare autosomal recessive disorder, which is caused by biallelic mutations in the highly conserved LYST gene. The disease is characterized by partial oculocut...
Source: Drug Discovery Today: Disease Models - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Animal and cell models for Lesch-Nyhan syndrome
Publication date: Available online 7 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Vanna Micheli, Gabriella Jacomelli, Annalisa Santucci, Giulia BernardiniLesch–Nyhan Disease (LND) is a rare X-linked recessive metabolic and neurological syndrome due to the deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). Peculiar neurological symptoms occur in LND: dystonia, choreoathetosis, compulsive self-injurious behaviour, with no obvious correlation to the deficiency of this purine salvage anzyme. A dopaminergic deficit was found to underlie the neurologic symptoms, but the aetiology fo...
Source: Drug Discovery Today: Disease Models - December 7, 2019 Category: Drugs & Pharmacology Source Type: research

The contribution of mouse models in the rare disease alkaptonuria
Publication date: Available online 5 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Juliette H. Hughes, George Bou-Gharios, Lakshminarayan R. Ranganath, James A. GallagherAlkaptonuria is an ultra-rare autosomal recessive disorder of tyrosine metabolism, whereby the homogentisate 1,2-dioxygenase (HGD) enzyme is deficient, causing an elevation of its substrate homogentisic acid (HGA). Overtime, elevated HGA causes connective tissue ochronosis, leading to a severe and early onset osteoarthropathy. The use of HGD deficient mouse models in this metabolic bone disease have provided the opportunity to investi...
Source: Drug Discovery Today: Disease Models - December 5, 2019 Category: Drugs & Pharmacology Source Type: research

Quantitative morphology of the lung and its importance in investigations of pulmonary diseases in mice
Publication date: Available online 28 November 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Wilfried KleinThe morphology of the mouse respiratory system has been studied in several different models of respiratory diseases, but quantitative morphological methods such as stereology are still only employed sporadically. This review discusses the use of stereology as a tool to understand the morphology of the mouse respiratory system and its link to the study of pulmonary mechanics. An integrated approach to study lung function in mice is being proposed, by combining non-invasive and invasive methods to analyze p...
Source: Drug Discovery Today: Disease Models - November 29, 2019 Category: Drugs & Pharmacology Source Type: research

Animal Models for Microbiome Research and Drug Discovery
Publication date: Summer 2018Source: Drug Discovery Today: Disease Models, Volume 28Author(s): Philip J. Richter, Pieter C. Dorrestein, Rob Knight (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Diaphragm muscle adaptations in health and disease
Publication date: Available online 27 November 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Matthew J. Fogarty, Gary C. SieckBreathing is achieved without thought despite being controlled by a complex neural network. The diaphragm is the predominant muscle responsible for force/pressure generation during breathing, but it is also involved in other non-ventilatory expulsive behaviors. This review considers alterations in diaphragm muscle fiber types and the neural control of the diaphragm across our lifespan and in various disease conditions. (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial to “Lung mechanics”
Publication date: Available online 3 November 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Wilfried Klein (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - November 4, 2019 Category: Drugs & Pharmacology Source Type: research

Analysis of respiratory mechanics in animal models: Its use in understanding lung behavior in emphysema and asthma
Publication date: Available online 29 October 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Paolo José Cesare Biselli, Julia Benini Kohler, Renato Righetti, Iolanda de Fátima Lopes Calvo Tibério, Mílton de Arruda Martins, Fernanda Degobbi Tenorio Quirino dos Santos LopesRespiratory mechanics assessment in animal models of respiratory diseases is considered a reliable tool to understand how structural changes impact lung function. Mathematical models, such as the equation of motion and the constant-phase model are used to describe the properties of the respiratory system. The equatio...
Source: Drug Discovery Today: Disease Models - October 30, 2019 Category: Drugs & Pharmacology Source Type: research

Wildlife-microbiome interactions and disease: exploring opportunities for disease mitigation across ecological scales
Publication date: Available online 4 October 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Candace L. Williams, Andrés Mauricio Caraballo-Rodríguez, Celeste Allaband, Amir Zarrinpar, Rob Knight, Julia M. GauglitzCaptive wildlife are a unique set of animals, whose diverse host–microbe symbioses are underexplored. Compared to their wild counterparts they are particularly susceptible to a variety of diseases, many of which have explicit or purported links to the microbiome. In this perspective, we will examine how the microbiome influences gastrointestinal disorders, metabolic dysregulation, r...
Source: Drug Discovery Today: Disease Models - October 5, 2019 Category: Drugs & Pharmacology Source Type: research

Animal models for understanding microbial decomposition of human remains
Publication date: Available online 30 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Aeriel D. Belk, Heather L. Deel, Zachary M. Burcham, Rob Knight, David O. Carter, Jessica L. MetcalfAnimal models are critical for forensic science research, particularly in studies of decomposition. This review examines the studies that have led to the development of using microbiome tools to predict the time since death, or postmortem interval (PMI), of human remains. Estimating PMI is crucial for forensic investigations, and most traditional tools are no longer effective after the first few days postmortem. The dev...
Source: Drug Discovery Today: Disease Models - October 2, 2019 Category: Drugs & Pharmacology Source Type: research

Ant microbial symbionts are a new model for drug discovery
Publication date: Available online 18 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Allan Artavia-León, Miguel Pacheco-Leiva, Cristofer Moya-Román, Natalia Rodríguez-Hernández, Adrián A. Pinto-TomásAnts have been widely studied, with 14,000 described species, but it is not until recently that they gained attention as sources for antimicrobial drug discovery. An increasing amount of studies are investigating ant-microbe symbioses, and clear benefits from their microbial counterparts have been experimentally demonstrated for ants in the tribes Attini, Camponoti...
Source: Drug Discovery Today: Disease Models - September 19, 2019 Category: Drugs & Pharmacology Source Type: research

Using gnotobiotic mice to discover and validate therapeutically active microbiota to maintain mucosal homeostasis and treat intestinal inflammation
Publication date: Available online 16 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): R. Balfour SartorStudies in gnotobiotic mice have dramatically expanded our understanding of the functional importance of microbiota in the pathogenesis of chronic intestinal inflammation. This brief review describes several strategies by which gnotobiotic mice models can be used to efficiently discover and validate protective components from the resident microbiota for potential therapeutic applications. We provide highly targeted examples of studies that use each of the various strategies to illustrate effective app...
Source: Drug Discovery Today: Disease Models - September 17, 2019 Category: Drugs & Pharmacology Source Type: research

Honey bee as a model organism to study gut microbiota and diseases
Publication date: Available online 14 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Xiaofei Wang, Xue Zhang, Zijing Zhang, Haoyu Lang, Hao ZhengHoney bee is used to model behavior, brain function, and life history transitions, and the physiology, genetics evolution, social behaviors have been intensively studied in this model organism. Recently, it shows that honeybees offer a particularly good opportunity to study the interactions between host biology and gut microbiota that are limited in complexity. All core members of the community are exclusive to this gut system, which are important to the host...
Source: Drug Discovery Today: Disease Models - September 14, 2019 Category: Drugs & Pharmacology Source Type: research

Use and limitations of noninvasive and invasive methods for studying pulmonary function
Publication date: Available online 11 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Juciane Maria de Andrade Castro, Momtchilo RussoThis mini-review aims to critically discuss the advantages and disadvantages of invasive versus noninvasive methods used to access pulmonary function especially in mice models of lung diseases. We briefly discussed the differences between both methods in handling expertise, number of mice required, length of time to determine lung function and anesthetic and/or use of muscle relaxant. Since noninvasive method received more criticisms than invasive method, we discussed cr...
Source: Drug Discovery Today: Disease Models - September 12, 2019 Category: Drugs & Pharmacology Source Type: research

Tunicates: A model organism to investigate the effects of associated-microbiota on the production of pharmaceuticals
Publication date: Available online 12 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Anelize Bauermeister, Paola Cristina Branco, Luciana Costa Furtado, Paula Christine Jimenez, Leticia Veras Costa-Lotufo, Tito Monteiro da Cruz LotufoAscidians are marine invertebrates closely related to vertebrates. These animals have been studied to address complex processes, including evolution of the immune system and developmental biology. As holobionts, housing millions of bacteria in a close relationship that drives adaptive fitness to environmental conditions, ascidians are successful invaders and dominant comp...
Source: Drug Discovery Today: Disease Models - September 12, 2019 Category: Drugs & Pharmacology Source Type: research

C. elegans and its bacterial diet: An interspecies model to explore the effects of microbiota on drug response
Publication date: Available online 5 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Cédric Diot, Aurian P. Garcia-Gonzalez, Albertha J.M. WalhoutOur body is inhabited by a large community of microorganisms referred to as our microbiota that influences almost all aspects of human physiology, including the response to thereapeutic drugs. Drugs can affect microbiota composition and the microbiota can modulate the drug response in the host. A major challenge is to determine which bacteria affect the response to which drugs, and to elucidate the mechanisms involved. Here, we discuss the emergence of...
Source: Drug Discovery Today: Disease Models - September 5, 2019 Category: Drugs & Pharmacology Source Type: research

Interactions between human microbiome, diet, enteric viruses and immune system: Novel insights from gnotobiotic pig research
Publication date: Available online 31 August 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Anastasia N. Vlasova, Gireesh Rajashekara, Linda J. SaifStudies over the past few decades demonstrated that gnotobiotic (Gn) pigs provide an unprecedented translational model to study human intestinal health and diseases. Due to the high degree of anatomical, physiological, metabolic, immunological, and developmental similarity, the domestic pig closely mimics the human intestinal microenvironment. Also, Gn piglets can be efficiently transplanted with human microbiota from infants, children and adults with resultant micr...
Source: Drug Discovery Today: Disease Models - September 1, 2019 Category: Drugs & Pharmacology Source Type: research

Without a bug’s life: Germ-free rodents to interrogate microbiota-gut-neuroimmune interactions
Publication date: Available online 30 August 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Simon Spichak, Katherine E. Guzzetta, Olivia F. O’Leary, Gerard Clarke, Timothy G. Dinan, John F. CryanThe human body harbors trillions of commensal microbes which play a crucial role in host development of the immune system, gastrointestinal tract, and brain. An alteration in the composition or function of these microbes has been implicated in numerous neurological, neuropsychological, and gastrointestinal diseases. The germ-free rodent model, devoid of all microbes, has been increasingly used to uncover the micro...
Source: Drug Discovery Today: Disease Models - August 31, 2019 Category: Drugs & Pharmacology Source Type: research

Using the natural variation of mouse populations to understand host-gut microbiome interactions
Publication date: Available online 29 August 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Elin Org, Aldons J. LusisOne approach to understanding gut microbiome–host interactions, described in this review, is to examine how natural variation in a model organism, where environmental factors can be controlled, affects the microbiome and, in turn, how the microbiome is associated with physiological or clinical traits. A variation of this approach, termed “systems genetics” is to characterize both the microbiome and the host using various high throughput technologies, such as metabolomics or gene...
Source: Drug Discovery Today: Disease Models - August 30, 2019 Category: Drugs & Pharmacology Source Type: research

Gut microbes as a therapeutic armory
Publication date: Available online 29 August 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Neerupma Bhardwaj, Naama Geva-ZatorskyGut microbes have recently been appreciated to be a possible source of future therapeutics. They have been shown to be associated with a variety of diseases from diverse etiologies. The microbiome can change during the progression of some diseases, and in some cases is linked with disease severity. Following these findings, fecal transplantation has been integrated into treating Clostridium difficile infections with high success rates. These results have become a driving force for st...
Source: Drug Discovery Today: Disease Models - August 30, 2019 Category: Drugs & Pharmacology Source Type: research

Model systems for the study of how symbiotic associations between animals and extracellular bacterial partners are established and maintained
Publication date: Available online 29 August 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Eric J. Koch, Margaret McFall-NgaiThis contribution describes the current state of experimental model development and use as a strategy for gaining insight into the form and function of certain types of host-microbe associations. Development of quality models for the study of symbiotic systems will be critical not only to facilitate an understanding of mechanisms underlying symbiosis, but also for providing insights into how drug development can promote healthy animal–microbe interactions as well as the treatment o...
Source: Drug Discovery Today: Disease Models - August 30, 2019 Category: Drugs & Pharmacology Source Type: research

Drosophila and its gut microbes: A model for drug-microbiome interactions
Publication date: Available online 24 August 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Angela E. DouglasDrosophila is an excellent system to investigate how the presence and composition of the gut microbiome influences the efficacy of therapeutic drugs and downstream consequences for host health. These opportunities derive from two key attributes of Drosophila. First, Drosophila is amenable for microbiome research, with simple, standardized methods to produce large numbers of microbiologically-sterile flies and flies with a standardized gut microbiome, thereby facilitating experimental reproducibility. Sec...
Source: Drug Discovery Today: Disease Models - August 26, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial: Models for Aging Research
Publication date: Spring 2018Source: Drug Discovery Today: Disease Models, Volume 27Author(s): Hildegard Mack (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - May 31, 2019 Category: Drugs & Pharmacology Source Type: research

Computational approaches for the systematic analysis of aging-associated molecular alterations
Publication date: Available online 28 April 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Cédric Debès, Ana Carolina Leote, Andreas BeyerAdvanced computational approaches are needed to interpret the data generated by high-throughput molecular profiling methods. This necessity is particularly pressing in the field of aging research because (i) it is challenging to separate causes and consequences of aging, (ii) samples are often very precious, thus reducing the number of biological replicates, and (iii) heterogeneity between replicates can be particularly high at old age. Here, we describe computa...
Source: Drug Discovery Today: Disease Models - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

Extracellular matrix components remodeling and lung function parameters in experimental emphysema and allergic asthma: Differences among the mouse strains
Publication date: Available online 20 April 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Milena Vasconcellos Oliveira, Pedro Leme Silva, Patricia Rieken Macedo RoccoMice are frequently used in experimental models of respiratory diseases due to their ease of manipulation, genetic homogeneity within inbred populations, and possibility of standardizing environmental exposures. However, it is well established that genetic strain variations in mice may exist, which imply changes in extracellular matrix (ECM) composition and degree of ECM remodeling, with potential for major impacts on respiratory mechanics. The lu...
Source: Drug Discovery Today: Disease Models - April 20, 2019 Category: Drugs & Pharmacology Source Type: research

The geometric framework: An approach for studying the impact of nutrition on healthy aging
Publication date: Available online 16 April 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Samantha M. Solon-Biet, Devin Wahl, David Raubenheimer, Victoria C. Cogger, David G. Le Couteur, Stephen J. SimpsonThe most robust interventions that impact on the biological processes of aging and age-related diseases are nutritional (caloric restriction, protein restriction, intermittent fasting) or those pharmacological and genetic interventions that act on nutrient sensing pathways. The best established nutritional intervention is caloric restriction, but this is not feasible in most humans; therefore, other nutrition...
Source: Drug Discovery Today: Disease Models - April 17, 2019 Category: Drugs & Pharmacology Source Type: research

Interstitial lung disease and surfactant dysfunction as a secondary manifestation of disease: insights from lysosomal storage disorders
Publication date: Available online 16 April 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Tamara L. Paget, Emma J. Parkinson-Lawrence, Sandra OrgeigLysosomal storage disorders are a group of genetic metabolic disorders caused by dysfunctional endosomal-lysosomal hydrolases, altered vesicular trafficking or biogenesis of the lysosome. This results in the accumulation of partially degraded substrates within cells, leading to abnormalities in multiple organ systems and reduced life expectancy. These diseases are chronic and progressive with the more severe cases experiencing the onset of disease symptoms early in...
Source: Drug Discovery Today: Disease Models - April 17, 2019 Category: Drugs & Pharmacology Source Type: research

A primer on ageing studies in mice: Considerations, opportunities and limitations
Publication date: Available online 23 February 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Paul K. PotterOne of the major challenges currently facing health care providers is an ageing population that is spending more time in ill-health. Many ageing individuals have multiple and complex needs which affect the ability to treat them effectively, which also has a significant impact on their own independence and quality of life. There are many aspects of testing interventions to improve health in old age in pre-clinical models; from breeding strategies to measurements of outcomes. Here we provide a brief overvie...
Source: Drug Discovery Today: Disease Models - February 23, 2019 Category: Drugs & Pharmacology Source Type: research

Human neurons to model aging: A dish best served old
Publication date: Available online 12 February 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Lena Böhnke, Larissa Traxler, Joseph R. Herdy, Jerome MertensWith the advancing age of humans and with it, growing numbers of age-related diseases, aging has become a major focus in recent research. The lack of fitting aging models, especially in neurological diseases where access to human brain samples is limited, has highlighted direct conversion into induced neurons (iN) as an important method to overcome this challenge. Contrary to iPSC reprogramming and its corresponding cell rejuvenation, the generation of i...
Source: Drug Discovery Today: Disease Models - February 13, 2019 Category: Drugs & Pharmacology Source Type: research

What have we learned so far on the molecular pathogenesis of Werner syndrome using mutant mouse models of this human progeroid disorder?
Publication date: Available online 12 January 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Michel Lebel, F. Brad JohnsonWerner syndrome (WS) is a rare autosomal recessive disorder characterized by genomic instability and the premature onset of several age-associated phenotypes. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA replication, repair, telomere maintenance, and transcription. This review focuses on experimental mouse models that have been generated to understand the molecular impact of different mutations in the Wrn orthologue on oxidative stress, inflammation, t...
Source: Drug Discovery Today: Disease Models - January 13, 2019 Category: Drugs & Pharmacology Source Type: research

The nematode Caenorhabditis elegans as a model for aging research
Publication date: Available online 6 January 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Hildegard I.D. Mack, Thomas Heimbucher, Coleen T. MurphyThe nematode Caenorhabditis elegans is a key model system for experimental research on the genetic regulation of aging, and has paved the way towards many important discoveries in this field. Importantly, in the course of its short lifespan of ∼3 weeks, C. elegans displays many phenotypic, behavioral, and molecular changes that are widely shared among metazoans as they age. In this review, we summarize how aging research takes advantage of C. elegans’ biol...
Source: Drug Discovery Today: Disease Models - January 6, 2019 Category: Drugs & Pharmacology Source Type: research

The African turquoise killifish Nothobranchius furzeri as a model for aging research
Publication date: Available online 6 January 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Hanna Reuter, Johannes Krug, Peter Singer, Christoph EnglertNothobranchius furzeri is an African killifish with an exceptionally short median life span of 3 to 7 months. Despite its short life span N. furzeri displays signs of aging that are highly reminiscent of mammalian aging. In 2015, reference sequences for the N. furzeri genome have been published. In addition, transgenesis and genomic engineering of killifish using CRISPR/Cas9 have been recently established. It has also been shown that N. furzeri is amenable to ph...
Source: Drug Discovery Today: Disease Models - January 6, 2019 Category: Drugs & Pharmacology Source Type: research

Models of neuroimmune and neurodegenerative diseases
Publication date: Winter 2017Source: Drug Discovery Today: Disease Models, Volumes 25–26Author(s): Sandra Amor (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - December 6, 2018 Category: Drugs & Pharmacology Source Type: research

Neural cell cultures to study spinal cord injury
Publication date: Available online 22 November 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): George A. McCanney, Michael J. Whitehead, Michael A. McGrath, Susan L. Lindsay, Susan C. BarnettThere are great challenges involved in identifying potential therapies for the repair of spinal cord injury (SCI). It is well accepted that not one, but a combination of therapeutic strategies will be required to effectively repair the damage. However, identifying novel therapeutics is hindered by the lack of reliable methods available that facilitate high throughput screening of numerous compounds. While the use of animals ...
Source: Drug Discovery Today: Disease Models - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

The ME7 prion model of neurodegeneration as a tool to understand and target neuroinflammation in Alzheimer’s disease
Publication date: Available online 22 November 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Joe K. Chouhan, Susan B. Fowler, Carl I. Webster, Jessica L. TeelingTo develop disease-modifying therapies for Alzheimer’s disease (AD), an understanding of the pathways that lead to synaptic damage and neuronal cell death is required. The ME7 prion mouse model shares hallmarks of human neurodegenerative diseases and has a well-defined disease progression that can be monitored non-invasively through changes in behaviour. In addition, a strong involvement of neuroinflammation in ME7 disease progression and systemi...
Source: Drug Discovery Today: Disease Models - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

Refinement of the MPTP model for Parkinson’s disease in the marmoset
Publication date: Available online 16 November 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Ingrid H.C.H.M PhilippensThe increasing prevalence of age-related neurodegenerative diseases is a growing concern for the ageing societies. Parkinson’s disease is a major progressive motor disorder of the brain caused by specific degeneration of the dopamine-producing neurons in the substantia nigra, which govern the control of muscle movement. Despite intensive research efforts, no cure has been found, and we still have to rely on symptom control treatment. The paucity of valid preclinical models that faithfully...
Source: Drug Discovery Today: Disease Models - November 17, 2018 Category: Drugs & Pharmacology Source Type: research

Mouse models of central nervous system ageing
Publication date: Available online 13 November 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Yang Heng, Bart J.L. Eggen, Erik W.G.M. Boddeke, Susanne M. KooistraAgeing is accompanied by decreased overall fitness and performance. Studying brain ageing in humans is challenging due to limited or no access to healthy tissue, limited opportunities for interventions and complicated confounding factors. The generation of mouse ageing models with uniform genetic backgrounds significantly contributed to understanding (brain) ageing at the molecular level. Research has focused on evolutionarily conserved mechanisms or p...
Source: Drug Discovery Today: Disease Models - November 14, 2018 Category: Drugs & Pharmacology Source Type: research

Modelling amyotrophic lateral sclerosis in mice
Publication date: Available online 30 October 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Jodie Stephenson, Sandra AmorAmyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease for which there is limited treatment. Riluzole, that extends life by several months, has been the only ALS drug for 22 years until the recent FDA approval of Edaravone. Despite many promising compounds identified in preclinical studies in the SOD1G93A mouse model, few have translated to the clinic. The failure to translate therapies in animals to people with ALS has questioned the validity of the SOD1G93A mouse mod...
Source: Drug Discovery Today: Disease Models - October 31, 2018 Category: Drugs & Pharmacology Source Type: research

Modelling in miniature: Using Drosophila melanogaster to study human neurodegeneration
Publication date: Available online 15 October 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Roald Lambrechts, Anita Faber, Ody SibonDespite great advances in clinical diagnostics, genetics and molecular biology, neurodegenerative diseases like Parkinson’s disease (PD), Alzheimer’s disease (AD) and Huntington’s disease (HD) still pose great challenges, both in terms of understanding their pathophysiology as well as their treatment. Organisms able to adequately model the intricacies of the disease mechanism and respose to potential treatment, whilst not compromising on ease of handling, studyin...
Source: Drug Discovery Today: Disease Models - October 16, 2018 Category: Drugs & Pharmacology Source Type: research

Cuprizone as a model of myelin and axonal damage
Publication date: Available online 15 October 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Stella Nyamoya, Felix Schweiger, Markus Kipp, Tanja HochstrasserAxonal damage is believed to be the main factor contributing to disease progression in multiple sclerosis patients. The degeneration of axons could be the result of several different harmful events including inflammation and demyelination. Details of the mechanisms leading to axonal damage are, however, unknown, and distinct preclinical animal models can be used to study mechanisms operant during axonal injury development and progression. In this review art...
Source: Drug Discovery Today: Disease Models - October 16, 2018 Category: Drugs & Pharmacology Source Type: research

Experimental models of cortical multiple sclerosis pathology
Publication date: Available online 11 October 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Maarten E. Witte, Jack van HorssenGrey matter tissue damage is a characteristic pathological hallmark of multiple sclerosis. Although evidence is emerging that cortical atrophy is strongly associated with sustained disease progression, the underlying pathological processes that contribute to neurodegeneration remain poorly understood. One reason for this is that key features of progressive MS, such as cortical demyelination, microglial cell activation and neurodegeneration are absent in most of the commonly used rodent ...
Source: Drug Discovery Today: Disease Models - October 12, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial to “Evaluating biomaterials and implanted devices”
Publication date: Summer 2017Source: Drug Discovery Today: Disease Models, Volume 24Author(s): Roberto Gaetani, Karen L. Christman (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - September 22, 2018 Category: Drugs & Pharmacology Source Type: research

Models for evaluating the immune response to naturally derived biomaterials
Publication date: Available online 2 August 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Jenna L. Dziki, Stephen F. BadylakThe immune response to biomaterials has emerged as a critical determinant of tissue repair outcomes and is complex, involving multiple cell types, distinct spatiotemporal phenotypes, and is influenced by variables including processing of the material and host-related factors. This interaction between implanted material and the host immune cells has stimulated interest in analytical methods to characterize the immune response. The present review discusses these methods including in vitro, ...
Source: Drug Discovery Today: Disease Models - August 3, 2018 Category: Drugs & Pharmacology Source Type: research