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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 iNs e...
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’ biology, a...
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 systemic in...
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 rep...
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, studying and manipu...
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