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Neurodegenerative disorder

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https://www.readbyqxmd.com/read/28943839/cellular-chaperones-as-therapeutic-targets-in-als-to-restore-protein-homeostasis-and-improve-cellular-function
#1
REVIEW
Bernadett Kalmar, Linda Greensmith
Heat shock proteins (Hsps) are ubiquitously expressed chaperone proteins that enable cells to cope with environmental stresses that cause misfolding and denaturation of proteins. With aging this protein quality control machinery becomes less effective, reducing the ability of cells to cope with damaging environmental stresses and disease-causing mutations. In neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), such mutations are known to result in protein misfolding, which in turn results in the formation of intracellular aggregates cellular dysfunction and eventual neuronal death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28943414/in-vivo-mri-assessment-of-the-human-locus-coeruleus-along-its-rostrocaudal-extent-in-young-and-older-adults
#2
Matthew J Betts, Arturo Cardenas-Blanco, Martin Kanowski, Frank Jessen, Emrah Düzel
The locus coeruleus (LC), a major origin of noradrenergic projections in the central nervous system (CNS), may serve a critical role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). As such, there is considerable interest to develop magnetic resonance imaging (MRI) techniques to assess the integrity of the LC in vivo. The high neuromelanin content of the LC serves as an endogenous contrast for MRI but existing protocols suffer from low spatial resolution along the rostrocaudal axis of the LC rendering it difficult to differentiate its integrity in caudal and rostral portions...
September 21, 2017: NeuroImage
https://www.readbyqxmd.com/read/28943274/gene-therapy-induced-antigen-specific-tregs-inhibit-neuro-inflammation-and-reverse-disease-in-a-mouse-model-of-multiple-sclerosis
#3
Geoffrey D Keeler, Sandeep Kumar, Brett Palaschak, Emily L Silverberg, David M Markusic, Noah T Jones, Brad E Hoffman
The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes...
September 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28943103/lower-vertebrate-and-invertebrate-models-of-alzheimer-s-disease-a-review
#4
REVIEW
Neha Sharma, Navneet Khurana, Arunachalam Muthuraman
Alzheimer's disease is a common neurodegenerative disorder which is characterized by the presence of beta- amyloid protein and neurofibrillary tangles (NFTs) in the brain. Till now, various higher vertebrate models have been in use to study the pathophysiology of this disease. But, these models possess some limitations like ethical restrictions, high cost, difficult maintenance of large quantity and lesser reproducibility. Besides, various lower chordate animals like Danio rerio, Drosophila melanogaster, Caenorhabditis elegans and Ciona intestinalis have been proved to be an important model for the in vivo determination of targets of drugs with least limitations...
September 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28942794/the-genetics-of-parkinson%C3%A2-disease
#5
Lina Mastrangelo
The 200years of research efforts on Parkinson disease (PD) form the basis of our understanding of the second most common neurodegenerative disorder after Alzheimer disease. This journey has been marked by the revolutionary discovery of a neurotransmitter replacement therapy that provides a longer and healthier life to patients. Since 1997, the advances in the genetics of PD have expanded our understanding of this neurodegenerative disorder and they are opening up new ways to search for disease-modifying therapies...
2017: Advances in Genetics
https://www.readbyqxmd.com/read/28942337/a-novel-approach-for-scrapie-associated-prion-prp-sc-detection-in-blood-using-the-competitive-affinity-of-an-aggregate-specific-antibody-and-streptavidin-to-prp-sc
#6
Andrei Soutyrine, Hongsheng Huang, Olga Andrievskaia, Ines Walther, Gordon Mitchell
Scrapie is a fatal neurodegenerative disorder affecting sheep and goats, originating from exposure to disease-associated prions (PrP(Sc)). An ante-mortem screening test that can detect native PrP(Sc) in body fluids remains unavailable due to insufficient sensitivity of current detection methods that involve proteinase or denaturation treatments. We adopted an approach to detect PrP(Sc) in whole blood using a simple proteinase- and denaturation-independent immunoassay, based on the competitive affinity of an aggregate-specific monoclonal antibody and streptavidin to PrP(Sc)...
September 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28942274/the-environmental-neurotoxin-%C3%AE-n-methylamino-l-alanine-l-bmaa-is-deposited-into-birds-eggs
#7
Marie Andersson, Oskar Karlsson, Ingvar Brandt
The neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disorders. BMAA is also a known developmental neurotoxin and research indicates that the sources of human and wildlife exposure may be more diverse than previously anticipated. The aim of the present study was therefore to examine whether BMAA can be transferred into birds' eggs. Egg laying quail were dosed with (14)C-labeled BMAA. The distribution of radioactivity in the birds and their laid eggs was then examined at different time points by autoradiography and phosphoimaging analysis...
September 20, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28942114/differentiation-of-mesenchymal-stem-cells-derived-trabecular-meshwork-into-dopaminergic-neuron-like-cells-on-nanofibrous-scaffolds
#8
Simin Jamali, Hossein Mostafavi, Ghasem Barati, Mehdi Eskandari, Samad Nadri
Parkinson's disease (PD) is a neurodegenerative disorder of the brain which is produced by the damage to dopaminergic neurons. Stem cell transplantation with a nanofibrous scaffold is one of the encouraging strategies for Parkinson's disease therapy. In this study, human mesenchymal stem cells (MSCs) from eye trabecular meshwork (TM) were differentiated into dopaminergic neurons on nanofibrous scaffold. After Trabecular meshwork biopsy, MSCs were isolated, cultivated on Poly-l-Lactide Acid (PLLA) nanofibrous scaffold (fabricated by electrospinning methods) and treated with medium containing DMEM supplemented with RA, IBMX and forskolin for 7 days...
September 20, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28940690/simple-strategy-for-sensitive-detection-of-dopamine-using-cdte-qds-modified-glassy-carbon-electrode
#9
Hong-Wei Yu, Ze Zhang, Jing-Hui Jiang, Hong-Zhi Pan, Dong Chang
BACKGROUND: Cellular and brain metabolism of dopamine can be correlated with a number of neurodegenerative disorders, our study was to explore a simple and efficient method to detect dopamine in real samples. METHODS: A new quantum dots (CdTe QDs) could be prepared using the hydrothermal method, the electrochemical biosensor was established by dropping CdTe QDs on the surface of glassy carbon electrode (GCE). RESULTS: The CdTe QDs/GCE exhibited the excellent electrochemical catalytic activity toward dopamine (DA) with good stability and high sensitivity in presence of interfering substances...
September 22, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28939959/population-base-rates-and-disease-course-of-common-psychiatric-and-neurodegenerative-disorders
#10
REVIEW
Katherine A Kitchen Andren, Nicolette M Gabel, Julija Stelmokas, Alyson M Rich, Linas A Bieliauskas
Knowledge of population base rates of neurological and psychiatric disorders is fundamental for diagnostic decision making. Consideration of relevant probabilistic information can improve diagnostic efficiency and accuracy. However, such data continue to be misused or underutilized, which can lead to misdiagnoses and negative patient outcomes. The aim of the current review is to create an easily accessible and comprehensive reference of existing age of onset as well as prevalence and incidence data for common neurodegenerative and psychiatric disorders in adults...
September 22, 2017: Neuropsychology Review
https://www.readbyqxmd.com/read/28939501/reprogramming-of-somatic-cells-to-induced-neural-stem-cells
#11
REVIEW
Ebrahim Shahbazi, Fahimeh Mirakhori, Vahid Ezzatizadeh, Hossein Baharvand
Recent investigations have demonstrated that defined sets of exogenous factors (chemical and/or biochemical) can convert human and mouse somatic cells into induced neural stem cells (iNSCs). Considering the self-renewal and multi-potential differentiation capabilities of iNSCs, generation of these cells has considerably enhanced cell therapy for treatment of neurodegenerative disorders. These cells can also serve as models for investigation of the mechanism(s) underlying neurodegenerative diseases and as an asset in drug discovery...
September 19, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28939187/the-ameliorative-effects-and-underlying-mechanisms-of-dopamine-d1-like-receptor-agonist-skf38393-on-a%C3%AE-1-42-induced-cognitive-impairment
#12
Xuan Zang, Zhao-Yan Cheng, Yi Sun, Nan Hua, Li-Hua Zhu, Ling He
Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles. It is the most common form of human cognitive decline and dementia. In this study, we aim to systematically investigate the ameliorative effects of dopamine D1-like receptor agonist SKF38393 on cognitive dysfunction and explore its underlying mechanisms. The Aβ1-42 was injected intracerebroventricularly to establish cognitive disorder model. Then, a series of behavior tests were used...
September 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28937953/the-biological-basis-of-chronic-traumatic-encephalopathy-following-blast-injury-a-literature-review
#13
Matt Aldag, Regina C Armstrong, Faris Bandak, Patrick S F Bellgowan, Timothy Bentley, Sean Biggerstaff, Katrina Caravelli, Joan Cmarik, Alicia Crowder, Thomas J DeGraba, Travis A Dittmer, Richard G Ellenbogen, Colin Greene, Raj K Gupta, Ramona Hicks, Stuart Hoffman, Robert C Latta, Michael J Leggieri, Donald Marion, Robert Mazzoli, Michael McCrea, John O'Donnell, Mark Packer, James B Petro, Todd E Rasmussen, Wendy Sammons-Jackson, Richard Shoge, Victoria Tepe, Ladd A Tremaine, James Zheng
The United States Department of Defense Blast Injury Research Program Coordinating Office organized the 2015 International State-of-the-Science meeting to explore links between blast-related head injury and the development of chronic traumatic encephalopathy (CTE). Before the meeting, the planning committee examined articles published between 2005 and October 2015 and prepared this literature review, which summarized broadly CTE research and addressed questions about the pathophysiological basis of CTE and its relationship to blast- and nonblast-related head injury...
September 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28936769/nlrp3-inflammasome-activation-in-a-transgenic-amyotrophic-lateral-sclerosis-model
#14
Agnese Gugliandolo, Sabrina Giacoppo, Placido Bramanti, Emanuela Mazzon
Amyotrophic lateral sclerosis (ALS) is a disabling progressive disease characterized by the degeneration of motor neurons, leading to muscle atrophy and paralysis. The majority of cases are sporadic, but also a familiar form of ALS exists, and some genes causative of the pathology were found. In particular, mutations in superoxide dismutase 1 (SOD1) were found in 20% of familiar cases. It is known that neuroinflammation plays a pivotal role in several neurodegenerative disorders, including ALS. Inflammasomes are protein complexes that induce inflammation in response to various stimuli, involved also in neuroinflammation...
September 21, 2017: Inflammation
https://www.readbyqxmd.com/read/28935901/a-brain-targeting-lipidated-peptide-for-neutralizing-rna-mediated-toxicity-in-polyglutamine-diseases
#15
Qian Zhang, Mengbi Yang, Kasper K Sørensen, Charlotte S Madsen, Josephine T Boesen, Ying An, Shao Hong Peng, Yuming Wei, Qianwen Wang, Knud J Jensen, Zhong Zuo, Ho Yin Edwin Chan, Jacky Chi Ki Ngo
Polyglutamine (PolyQ) diseases are progressive neurodegenerative disorders caused by both protein- and RNA-mediated toxicities. We previously showed that a peptidyl inhibitor, P3, which binds directly to expanded CAG RNA can inhibit RNA-induced nucleolar stress and suppress RNA-induced neurotoxicity. Here we report a N-acetylated and C-amidated derivative of P3, P3V8, that showed a more than 20-fold increase in its affinity for expanded CAG RNA. The P3V8 peptide also more potently alleviated expanded RNA-induced cytotoxicity in vitro, and suppressed polyQ neurodegeneration in Drosophila with no observed toxic effects...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934429/gene-expression-analysis-reveals-genes-common-to-cerebral-malaria-and-neurodegenerative-disorders
#16
Sandrine Cabantous, Ogobara Doumbo, Belco Poudiougou, Laurence Louis, Abdoulaye Barry, Aboubacar A Oumar, Abdoualye Traore, Sandrine Marquet, Alain Dessein
Cerebral malaria, a reversible encephalopathy affecting young children, is a medical emergency requiring urgent clinical assessment and treatment. We performed a whole-transcriptomic analysis of blood samples from Malian children with cerebral or uncomplicated malaria. We focused on transcripts from pathways for which dysfunction has been associated with neurodegenerative disorders. We found that SNCA, SIAH2, UBB, HSPA1A, TUBB2A, and PINK1 were upregulated (fold-increases, ≥2.6), whereas UBD and PSMC5 were downregulated (fold-decreases, ≤4...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934390/protein-phosphatase-1-regulates-huntingtin-exon-1-aggregation-and-toxicity
#17
Joana Branco-Santos, Federico Herrera, Gonçalo M Poças, Yolanda Pires-Afonso, Flaviano Giorgini, Pedro M Domingos, Tiago F Outeiro
Huntington's disease is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregation and toxicity in human cells and Drosophila neurons. We used bimolecular fluorescence complementation to show that expression of single phosphomimic mutations completely abolished HTTex1 aggregation in human cells...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28933978/the-glycosidase-treatment-of-gentianae-scabrae-radix-converts-trifloroside-into-deglucosyltrifloroside-with-an-enhancement-of-antioxidative-effects
#18
Eun-Ju Yang, Ju-Gyeong Lee, Kyung-Sik Song
Herbal medicines were subjected to enzyme reaction by using a commercial glycosidase AMG-300L, and were evaluated for enhancement of their antioxidative activities. The methanolic extract of Gentianae Scabrae Radix (GSR) showed the most dramatic changes after enzyme reaction, as seen in the high-performance liquid chromatography profiles and an increase in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect. Trifloroside (1, TF) was identified as being significantly decreased by enzyme reaction, whereas deglucosyltrifloroside (2, DTF) increased...
September 21, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28933595/phosphoproteome-based-kinase-activity-profiling-reveals-the-critical-role-of-map2k2-and-plk1-in-neuronal-autophagy
#19
Lei-Lei Chen, Yong-Bo Wang, Ju-Xian Song, Wan-Kun Deng, Jia-Hong Lu, Li-Li Ma, Chuan-Bin Yang, Min Li, Yu Xue
Recent studies have demonstrated that dysregulation of macroautophagy/autophagy may play a central role in the pathogenesis of neurodegenerative disorders, and the induction of autophagy protects against the toxic insults of aggregate-prone proteins by enhancing their clearance. Thus, autophagy has become a promising therapeutic target against neurodegenerative diseases. In this study, quantitative phosphoproteomic profiling together with a computational analysis was performed to delineate the phosphorylation signalling networks regulated by 2 natural neuroprotective autophagy enhancers, corynoxine (Cory) and corynoxine B (Cory B)...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933327/concussion-in-sports-what-trauma-orthopedic-surgeons-need-to-know
#20
A Gänsslen, T Neubauer, W Krutsch
Concussion in sport is often underdiagnosed with the potential risk of long-term sequelae. This article presents the mechanisms, the underlying pathophysiology and typical primary signs and symptoms. The recognition and resulting medical measures including the present recommendations and decisions on return to play are described. The majority of patients with concussion present with clinical and cognitive symptoms only for short time intervals. As a rule a complete subjective recovery is observed within a few hours or days...
2017: Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca
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