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Neurodegenerative diseases

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https://www.readbyqxmd.com/read/28931001/an-automated-rapid-iterative-negative-geotaxis-assay-for-analyzing-adult-climbing-behavior-in-a-drosophila-model-of-neurodegeneration
#1
Wenze Cao, Li Song, Jingjing Cheng, Na Yi, Luyi Cai, Fu-de Huang, Margaret Ho
Neurodegenerative diseases are frequently associated with a progressive loss of movement ability, reduced life span, and age-dependent neurodegeneration. To understand the mechanism of these cellular events, and their causal relationships with each other, Drosophila melanogaster, with its sophisticated genetic tools and diverse behavioral features, are used as disease models for assessing neurodegenerative phenotypes. Here we describe a high-throughput method to analyze Drosophila adult negative geotaxis behavior, as an indication for possible motor defects associated with neurodegeneration...
September 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930984/high-fat-diet-feeding-and-high-throughput-triacylglyceride-assay-in-drosophila-melanogaster
#2
Soda Balla Diop, Ryan T Birse, Rolf Bodmer
Heart disease is the number one cause of human death worldwide. Numerous studies have shown strong connections between obesity and cardiac malfunction in humans, but more tools and research efforts are needed to better elucidate the mechanisms involved. For over a century, the genetically highly tractable model of Drosophila has been instrumental in the discovery of key genes and molecular pathways that proved to be highly conserved across species. Many biological processes and disease mechanisms are functionally conserved in the fly, such as development (e...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930690/the-self-inactivating-kamicas9-system-for-the-editing-of-cns-disease-genes
#3
Nicolas Merienne, Gabriel Vachey, Lucie de Longprez, Cécile Meunier, Virginie Zimmer, Guillaume Perriard, Mathieu Canales, Amandine Mathias, Lucas Herrgott, Tim Beltraminelli, Axelle Maulet, Thomas Dequesne, Catherine Pythoud, Maria Rey, Luc Pellerin, Emmanuel Brouillet, Anselme L Perrier, Renaud du Pasquier, Nicole Déglon
Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expression of the Cas9 protein and high editing efficiency. In the first application, the gene responsible for Huntington's disease (HD) was targeted in adult mouse neuronal and glial cells. Mutant huntingtin (HTT) was efficiently inactivated in mouse models of HD, leading to an improvement in key markers of the disease...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#4
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930607/transcriptomics-in-amyotrophic-lateral-sclerosis
#5
Marios G Krokidis, Panagiotis Vlamos
Amyotrophic lateral sclerosis (ALS) is an adult-onset, incurable neurodegenerative disease characterized by the selective death of upper and lowers motor neurons in the spinal cord, brainstem and motor cortex, which ultimately leads to paralysis and death within 2-3 years of onset. ALS is poorly understood, although multiple studies have been proposed to explain the pathophysiological mechanisms of the disorder. The development of microarray technology, for simultaneous analysis of the transcriptional expression of thousands of genes, has provided new possibilities to get better insights into the pathogenesis of ALS, and most important, potential new candidate targets for novel treatments...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28930568/medical-imaging-diagnosis-of-early-alzheimer-s-disease
#6
Fatma El-Zahraa A El-Gamal, Mohammed M Elmogy, Mohammed Ghazal, Ahmed Atwan, Manual F Casanova, Gregory N Barnes, Ayman El-Baz, Hassan Hajjdiab
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases that influences the central nervous system, often leading to dire consequences for quality of life. The disease goes through some stages mainly divided into early, moderate, and severe. Among them, the early stage is the most important as medical intervention has the potential to alter the natural progression of the condition. In practice, the early diagnosis is a challenge since the neurodegenerative changes can precede the onset of clinical symptoms by 10-15 years...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930527/microalgae-as-a-source-of-high-value-bioactive-compounds
#7
Mohammed Hussen Bule, Ishtiaq Ahmed, Faheem Maqbool, Muhammad Bilal, Hafiz M N Iqbal
Microalgae are one of the oldest microorganisms, that grow in various hostile environments, ranging from deserts to Antarctica. The microalgae sustain life in such harsh environments through generation of secondary metabolites. Microalgae biosynthesize a large number of diverse bioactive metabolites with activities on cancer, neurodegenerative diseases, and infectious diseases. Here, we highlight the bioactive compounds that are isolated from microalgae for the purpose of using them as food, and as chemicals in pharmaceutical industry as new agents with therapeutic benefits...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28929759/selective-inhibitors-of-dual-leucine-zipper-kinase-dlk-map3k12-with-activity-in-a-model-of-alzheimer-s-disease
#8
Snahel Patel, William J Meilandt, Rebecca I Erickson, Jinhua Chen, Gauri Deshmukh, Anthony A Estrada, Reina N Fuji, Paul Gibbons, Amy Gustafson, Seth F Harris, Jose Imperio, Wendy Liu, Xingrong Liu, Yichin Liu, Joseph P Lyssikatos, Changyou Ma, Jianping Yin, Joseph W Lewcock, Michael Siu
Significant data exists to suggest that dual leucine zipper kinase (DLK, MAP3K12) is a conserved regulator of neuronal degeneration following neuronal injury and in chronic neurodegenerative disease. Consequently, there is considerable interest in the identification of DLK inhibitors with a profile compatible with development for these indications. Herein, we use structure-based drug design combined with a focus on CNS drug-like properties to generate compounds with superior kinase selectivity and metabolic stability as compared to previously disclosed DLK inhibitors...
September 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28929453/effects-of-long-term-ingestion-of-white-tea-on-oxidation-produced-by-aging-and-acute-oxidative-damage-in-rats
#9
Cristóbal Espinosa Ruiz, Lorena Cabrera, José Ángel López-Jiménez, Salvador Zamora, Francisca Pérez-Llamas
The infusion tea extracted from the leaves of the plant Camellia sinensis can be used in the prevention of cancer, cardiovascular and neurodegenerative diseases, and aging, while adriamycin (ADR) is an anticancer drug that increases oxidative stress in cells. The present study evaluated the protective effect of the long-term consumption of white tea used at two different doses against the oxidative stress produced by aging and acute oxidation caused ADR treatment. At wearing, rats received distilled water (control), or 0...
September 19, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28929442/the-role-of-methionine-on-metabolism-oxidative-stress-and-diseases
#10
REVIEW
Yordan Martínez, Xue Li, Gang Liu, Peng Bin, Wenxin Yan, Dairon Más, Manuel Valdivié, Chien-An Andy Hu, Wenkai Ren, Yulong Yin
Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases...
September 19, 2017: Amino Acids
https://www.readbyqxmd.com/read/28929132/interplay-between-protein-glycosylation-pathways-in-alzheimer-s-disease
#11
Moran Frenkel-Pinter, Merav Daniel Shmueli, Chen Raz, Michaela Yanku, Shai Zilberzwige, Ehud Gazit, Daniel Segal
Deviations from the normal nucleoplasmic protein O-GlcNAcylation, as well as from normal protein sialylation and N-glycosylation in the secretory pathway, have been reported in Alzheimer's disease (AD). However, the interplay between the cytoplasmic protein O-GlcNAcylation and the secretory N-/O-glycosylation in AD has not been described. We present a comprehensive analysis of the N-, O-, and O-GlcNAc-glycomes in AD-affected brain regions as well as in AD patient serum. We detected marked differences in levels of glycan involved in both protein O-GlcNAcylation and N-/O-glycosylation between patients and healthy individuals and revealed brain region-specific glycosylation-related pathology in patients...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28929129/an-automated-home-cage-system-to-assess-learning-and-performance-of-a-skilled-motor-task-in-a-mouse-model-of-huntington-s-disease
#12
Cameron L Woodard, Federico Bolaños, James D Boyd, Gergely Silasi, Timothy H Murphy, Lynn A Raymond
Behavioral testing is a critical step in assessing the validity of rodent models of neurodegenerative disease, as well as evaluating the efficacy of pharmacological interventions. In models of Huntington's disease (HD), a gradual progression of impairments is observed across ages, increasing the need for sensitive, high-throughput and longitudinal assessments. Recently, a number of automated systems have been developed to perform behavioral profiling of animals within their own home-cage, allowing for 24-h monitoring and minimizing experimenter interaction...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28928962/current-concepts-and-controversies-in-the-pathogenesis-of-parkinson-s-disease-dementia-and-dementia-with-lewy-bodies
#13
REVIEW
Rimona S Weil, Tammaryn L Lashley, Jose Bras, Anette E Schrag, Jonathan M Schott
Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are relentlessly progressive neurodegenerative disorders that are likely to represent two ends of a disease spectrum. It is well established that both are characterised pathologically by widespread cortical Lewy body deposition. However, until recently, the pathophysiological mechanisms leading to neuronal damage were not known. It was also not understood why some cells are particularly vulnerable in PDD/DLB, nor why some individuals show more aggressive and rapid dementia than others...
2017: F1000Research
https://www.readbyqxmd.com/read/28928905/fucoxanthin-a-marine-carotenoid-attenuates-%C3%AE-amyloid-oligomer-induced-neurotoxicity-possibly-via-regulating-the-pi3k-akt-and-the-erk-pathways-in-sh-sy5y-cells
#14
Jiajia Lin, Jie Yu, Jiaying Zhao, Ke Zhang, Jiachen Zheng, Jialing Wang, Chunhui Huang, Jingrong Zhang, Xiaojun Yan, William H Gerwick, Qinwen Wang, Wei Cui, Shan He
Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by neurofibrillary tangles, synaptic impairments, and loss of neurons. Oligomers of β-amyloid (Aβ) are widely accepted as the main neurotoxins to induce oxidative stress and neuronal loss in AD. In this study, we discovered that fucoxanthin, a marine carotenoid with antioxidative stress properties, concentration dependently prevented Aβ oligomer-induced increase of neuronal apoptosis and intracellular reactive oxygen species in SH-SY5Y cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28928628/axonal-degeneration-during-aging-and-its-functional-role-in-neurodegenerative-disorders
#15
REVIEW
Natalia Salvadores, Mario Sanhueza, Patricio Manque, Felipe A Court
Aging constitutes the main risk factor for the development of neurodegenerative diseases. This represents a major health issue worldwide that is only expected to escalate due to the ever-increasing life expectancy of the population. Interestingly, axonal degeneration, which occurs at early stages of neurodegenerative disorders (ND) such as Alzheimer's disease, Amyotrophic lateral sclerosis, and Parkinson's disease, also takes place as a consequence of normal aging. Moreover, the alteration of several cellular processes such as proteostasis, response to cellular stress and mitochondrial homeostasis, which have been described to occur in the aging brain, can also contribute to axonal pathology...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28928221/upregulation-of-autophagy-related-gene-5-protects-dopaminergic-neurons-in-a-zebrafish-model-of-parkinson-s-disease
#16
Zhan-Ying Hu, Bo Chen, Jing-Pu Zhang, Yuan-Yuan Ma
Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases, and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928079/polyglutamine-expansion-diseases-more-than-simple-repeats
#17
Alexandra Silva, Ana Viana de Almeida, Sandra Macedo-Ribeiro
Polyglutamine (polyQ) repeat-containing proteins are widespread in the human proteome but only nine of them are associated with highly incapacitating neurodegenerative disorders. The genetic expansion of the polyQ tract in disease-related proteins triggers a series of events resulting in neurodegeneration. The polyQ tract plays the leading role in the aggregation mechanism, but other elements modulate the aggregation propensity in the context of the full-length proteins, as implied by variations in the length of the polyQ tract required to trigger the onset of a given polyQ disease...
September 16, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28927992/protective-effects-of-the-glp-1-mimetic-exendin-4-in-parkinson-s-disease
#18
REVIEW
Dilan Athauda, Thomas Foltynie
There is increasing interest in the potential role of glucagon-like peptide-1 (GLP-1) receptor agonists as neuroprotective treatments in neurodegenerative diseases including Parkinson's disease following the publication of the results of the Exenatide-PD trial. Of the current GLP-1 receptor agonists already licensed to treat Type 2 diabetes several including exenatide, liraglutide and lixisenatide are the subject of ongoing clinical trials in PD. The underlying rationale for using drugs licensed and effective for T2DM in PD patients therefore needs to be scrutinized, and the results obtained to date critically reviewed...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28927719/sex-dependent-behavioral-impairments-in-the-hdhq350-mouse-line
#19
Jessica K Cao, Peter J Detloff, Richard G Gardner, Nephi Stella
Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease characterized by gradual deterioration of motor and cognitive functions and development of psychiatric deficits. Animal models provide powerful means to study the pathological processes, molecular dysfunctions and symptoms associated with HD. We performed a longitudinal behavioral study of the newly developed HdhQ350/+ mouse line, a knock-in model that expresses a repeat of 350 glutamines. We found remarkable sex-dependent differences on symptom onset and severity...
September 16, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28927418/a-systematic-review-and-integrative-approach-to-decode-the-common-molecular-link-between-levodopa-response-and-parkinson-s-disease
#20
Debleena Guin, Manish Kumar Mishra, Puneet Talwar, Chitra Rawat, Suman S Kushwaha, Shrikant Kukreti, Ritushree Kukreti
BACKGROUND: PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly inconclusive. Here, we aim to identify predictive genetic biomarkers for levodopa response (LR) and determine common molecular link with disease susceptibility. A systematic review for LR was conducted for ADR, and drug efficacy, independently. All included articles were assessed for methodological quality on 14 parameters...
September 19, 2017: BMC Medical Genomics
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