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https://www.readbyqxmd.com/read/29677544/peptide-based-therapeutics-and-their-use-for-the-treatment-of-neurodegenerative-and-other-diseases
#1
REVIEW
Mohammad Hassan Baig, Khurshid Ahmad, Mohd Saeed, Ahmed M Alharbi, George E Barreto, Ghulam Md Ashraf, Inho Choi
Bioactive peptides are actively involved in different biological functions and importantly contribute to human health, and the use of peptides as therapeutics has a long successful history in disease management. A number of peptides have wide-ranging therapeutic effects, such as antioxidant, antimicrobial, and antithrombotic effects. Neurodegenerative diseases are typically caused by abnormal aggregations of proteins or peptides, and the depositions of these aggregates in or on neurons, disrupt signaling and eventually kill neurons...
April 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29677512/nuclear-import-receptors-reverse-aberrant-phase-transitions-of-rna-binding-proteins-with-prion-like-domains
#2
Lin Guo, Hong Joo Kim, Hejia Wang, John Monaghan, Fernande Freyermuth, Julie C Sung, Kevin O'Donovan, Charlotte M Fare, Zamia Diaz, Nikita Singh, Zi Chao Zhang, Maura Coughlin, Elizabeth A Sweeny, Morgan E DeSantis, Meredith E Jackrel, Christopher B Rodell, Jason A Burdick, Oliver D King, Aaron D Gitler, Clotilde Lagier-Tourenne, Udai Bhan Pandey, Yuh Min Chook, J Paul Taylor, James Shorter
RNA-binding proteins (RBPs) with prion-like domains (PrLDs) phase transition to functional liquids, which can mature into aberrant hydrogels composed of pathological fibrils that underpin fatal neurodegenerative disorders. Several nuclear RBPs with PrLDs, including TDP-43, FUS, hnRNPA1, and hnRNPA2, mislocalize to cytoplasmic inclusions in neurodegenerative disorders, and mutations in their PrLDs can accelerate fibrillization and cause disease. Here, we establish that nuclear-import receptors (NIRs) specifically chaperone and potently disaggregate wild-type and disease-linked RBPs bearing a NLS...
April 19, 2018: Cell
https://www.readbyqxmd.com/read/29677367/stable-microsaccades-and-microsaccade-induced-global-alpha-band-phase-reset-across-the-life-span
#3
Ying Gao, Carl Huber, Bernhard A Sabel
Purpose: To understand the effect of aging on microsaccade functions and brain physiologic responses, we quantified microsaccades and their physiologic correlates (including their interaction with alpha band brain oscillation) in normal subjects of different ages. Methods: Twenty-two normally sighted young (18 to 29 years), 22 middle-aged (31 to 55 years), and 22 elderly subjects (56 to 77 years) participated in this cross-sectional study. Dense array EEG and high-resolution eye-tracking data were simultaneously recorded during a fixation task...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29677167/the-role-of-catechins-in-cellular-responses-to-oxidative-stress
#4
REVIEW
Jurga Bernatoniene, Dalia Marija Kopustinskiene
Catechins are polyphenolic compounds—flavanols of the flavonoid family found in a variety of plants. Green tea, wine and cocoa-based products are the main dietary sources of these flavanols. Catechins have potent antioxidant properties, although in some cases they may act in the cell as pro-oxidants. Catechins are reactive oxygen species (ROS) scavengers and metal ion chelators, whereas their indirect antioxidant activities comprise induction of antioxidant enzymes, inhibition of pro-oxidant enzymes, and production of the phase II detoxification enzymes and antioxidant enzymes...
April 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29677102/implications-of-pi3k-akt-pten-signaling-on-superoxide-dismutases-expression-and-in-the-pathogenesis-of-alzheimer-s-disease
#5
REVIEW
Satoru Matsuda, Yukie Nakagawa, Ai Tsuji, Yasuko Kitagishi, Atsuko Nakanishi, Toshiyuki Murai
Alzheimer’s disease is a neurodegenerative sickness, where the speed of personal disease progression differs prominently due to genetic and environmental factors such as life style. Alzheimer’s disease is described by the construction of neuronal plaques and neurofibrillary tangles composed of phosphorylated tau protein. Mitochondrial dysfunction may be a noticeable feature of Alzheimer’s disease and increased production of reactive oxygen species has long been described. Superoxide dismutases (SODs) protect from excess reactive oxygen species to form less reactive hydrogen peroxide...
April 20, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29676481/high-mobility-group-box-1-in-parkinson-s-disease-from-pathogenesis-to-therapeutic-approaches
#6
REVIEW
Efthalia Angelopoulou, Christina Piperi, Athanasios G Papavassiliou
Parkinson's disease (PD) presents the second most common neurodegenerative disorder with largely unknown pathogenesis and inefficient therapeutic management. Accumulating data indicate that neuroinflammation, autophagy impairment, α-synuclein aggregation and mitochondrial dysfunction may contribute to PD onset; however the molecular mechanisms underlying these pathophysiological processes are still under elucidation. Interestingly, recent evidence has indicated that High-mobility group box 1 (HMGB1), a DNA-binding protein that can be actively secreted by inflammatory cells and passively released by necrotic cells may play a key role in PD pathogenesis...
April 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29676231/combating-neurodegenerative-diseases-with-the-plant-alkaloid-berberine-molecular-mechanisms-and-therapeutic-potential
#7
Dahua Fan, Liping Liu, Zhengzhi Wu, Meiqun Cao
Neurodegenerative diseases are among the most serious health problems affecting millions of people worldwide. Such diseases are characterized by a progressive degeneration and / or death of neurons in the central nervous system. Currently, there are no therapeutic approaches to cure or even halt the progression of neurodegenerative diseases. During the last two decades, much attention has been paid to the neuroprotective and anti-neurodegenerative activities of compounds isolated from natural products with high efficacy and low toxicity...
April 19, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29676205/effects-of-peptidyl-prolyl-isomerase-1-depletion-in-animal-models-of-prion-diseases
#8
Giuseppe Legname, Tommaso Virgilio, Edoardo Bistaffa, Chiara Maria Giulia De Luca, Marcella Catania, Paola Zago, Elisa Isopi, Ilaria Campagnani, Fabrizio Tagliavini, Giorgio Giaccone, Fabio Moda
Pin1 is a peptidyl-prolyl isomerase that induces the cis-trans conversion of specific Ser/Thr-Pro peptide bonds in phosphorylated proteins, leading to conformational changes through which Pin1 regulates protein stability and activity. Since down-regulation of Pin1 has been described in several neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), we investigated its potential role in prion diseases. Animals generated on wild-type (Pin1+/+ ), hemizygous (Pin1+/- ) or knock-out (Pin1-/- ) background for Pin1 were experimentally infected with RML prions...
April 20, 2018: Prion
https://www.readbyqxmd.com/read/29676181/identification-of-glia-phenotype-modulators-based-on-select-glial-function-regulatory-signaling-pathways
#9
Sun-Hwa Lee, Kyoungho Suk
Despite the considerable social and economic burden on the healthcare system worldwide due to neurodegenerative diseases, there are currently few disease-altering treatment options for many of these conditions. Therefore, new approaches for both prevention and intervention for neurodegenerative diseases are urgently required. Microglia-mediated neurotoxicity is one of the pathologic hallmarks common to Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Current therapeutic approaches to target microglia-mediated neurotoxicity are focused on the identification of glia phenotype modulators (GPMs), which can inhibit the 'classical' pro-inflammatory and neurotoxic phenotypes of microglia...
April 20, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29676170/discovery-of-novel-dual-acetylcholinesterase-inhibitors-with-antifibrillogenic-activity-related-to-alzheimer-s-disease
#10
Jonathan R de Almeida, Micheli Figueiro, Wanda Pereira Almeida, Carlos Henrique Tomich de Paula da Silva
AIM: Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting elderly people. The current pharmacological approach is based on the improvement of cholinergic neurotransmission by inhibiting acetylcholinesterase (AChE) with AChE inhibitors. The disease is also characterized by the accelerated accumulation of β-amyloid plaques around neurons. Furthermore, in vitro studies revealed that AChE can induce β-amyloid peptide (Aβ) aggregation. METHODOLOGY: Computer-aided molecular design by virtual screening was here employed to discover novel potential AChE inhibitors, with antifibrillogenic properties, in other words, inhibiting Aβ aggregation...
April 20, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29675823/impact-of-neurodegenerative-diseases-on-drug-binding-to-brain-tissues-from-animal-models-to-human-samples
#11
Ana Ugarte, David Corbacho, María S Aymerich, Ana García-Osta, Mar Cuadrado-Tejedor, Julen Oyarzabal
Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD)...
April 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29675785/neuronal-autophagy-and-axon-degeneration
#12
REVIEW
Yu Wang, Mingxue Song, Fuyong Song
Axon degeneration is a pathophysiological process of axonal dying and breakdown, which is characterized by several morphological features including the accumulation of axoplasmic organelles, disassembly of microtubules, and fragmentation of the axonal cytoskeleton. Autophagy, a highly conserved lysosomal-degradation machinery responsible for the control of cellular protein quality, is widely believed to be essential for the maintenance of axonal homeostasis in neurons. In recent years, more and more evidence suggests that dysfunctional autophagy is associated with axonal degeneration in many neurodegenerative diseases...
April 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29675716/disturbances-of-sleep-and-alertness-in-parkinson-s-disease
#13
REVIEW
Aleksandar Videnovic
PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Sleep dysfunction is one of the most common non-motor manifestations of PD that has gained significant interest over the past two decades due to its impact on the daily lives of PD patients, poorly understood mechanisms, and limited treatment options. In this review, we discuss the most common sleep disorders in PD and present recent investigations that have broadened our understanding of the epidemiology, clinical manifestations, diagnosis, and treatment of disturbed sleep and alertness in PD...
April 19, 2018: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/29675426/a-novel-method-for-drug-screen-to-regulate-g-protein-coupled-receptors-in-the-metabolic-network-of-alzheimer-s-disease
#14
Yang Li, Wei Zheng, Wuyun Qiqige, Shujuan Cao, Jishou Ruan, Yanping Zhang
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder and the pathogenesis of AD is poorly understood. G protein-coupled receptors (GPCRs) are involved in numerous key AD pathways and play a key role in the pathology of AD. To fully understand the pathogenesis of AD and design novel drug therapeutics, analyzing the connection between AD and GPCRs is of great importance. In this paper, we firstly build and analyze the AD-related pathway by consulting the KEGG pathway of AD and a mass of literature and collect 25 AD-related GPCRs for drug discovery...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29675083/neuroimaging-in-menkes-disease
#15
Molla I Ahmed, Nahin Hussain
Menkes disease (MD) is a rare infantile onset neurodegenerative disorder due to mutations in the X linked ATP7A gene. These patients can present with failure to thrive, severe psychomotor retardation, seizures and hypopigmented hair, which is characteristic of this condition. A number of neuro-radiological findings have been reported in this condition. We report the spectrum of neuro-radiological findings in three affected boys being treated at our centre. We suggest that magnetic resonance imaging (MRI) and, in particular magnetic resonance angiography (MRA) when taken in the context of the clinical presentation may be helpful in making an early diagnosis of this devastating condition...
October 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/29674596/mfn2-agonists-reverse-mitochondrial-defects-in-preclinical-models-of-charcot-marie-tooth-disease-type-2a
#16
Agostinho G Rocha, Antonietta Franco, Andrzej M Krezel, Jeanne M Rumsey, Justin M Alberti, William C Knight, Nikolaos Biris, Emmanouil Zacharioudakis, James W Janetka, Robert H Baloh, Richard N Kitsis, Daria Mochly-Rosen, R Reid Townsend, Evripidis Gavathiotis, Gerald W Dorn
Mitofusins (MFNs) promote fusion-mediated mitochondrial content exchange and subcellular trafficking. Mutations in Mfn2 cause neurodegenerative Charcot-Marie-Tooth disease type 2A (CMT2A). We showed that MFN2 activity can be determined by Met376 and His380 interactions with Asp725 and Leu727 and controlled by PINK1 kinase-mediated phosphorylation of adjacent MFN2 Ser378 Small-molecule mimics of the peptide-peptide interface of MFN2 disrupted this interaction, allosterically activating MFN2 and promoting mitochondrial fusion...
April 20, 2018: Science
https://www.readbyqxmd.com/read/29673962/orexin-receptor-expression-is-increased-during-mancozeb-induced-feeding-impairments-and-neurodegenerative-events-in-a-marine-fish
#17
Merylin Zizza, Mariana Di Lorenzo, Vincenza Laforgia, Emilia Furia, Giovanni Sindona, Marcello Canonaco, Rosa Maria Facciolo
Food intake ensures energy resources sufficient for basic metabolism, immune system and reproductive investment. It is already known that food-seeking performances, which are crucially controlled by orexins (ORXs), may be under the influence of environmental factors including pollutants. Among these, mancozeb (mz) is becoming an environmental risk for neurodegenerative diseases. Due to few studies on marine fish exposed to mz, it was our intention to correlate feeding latency, food intake and feeding duration to potential neurodegenerative processes in key diencephalic sites and expression changes of the ORX neuroreceptor (ORXR) in the ornate wrasses (Thalassoma pavo)...
April 16, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29673913/epothilone-d-inhibits-microglia-mediated-spread-of-alpha-synuclein-aggregates
#18
Dario Valdinocci, Gary Grant, Tracey Dickson, Dean L Pountney
Multiple System Atrophy (MSA) is a progressive neurodegenerative disease characterized by chronic neuroinflammation and widespread α-synuclein (α-syn) cytoplasmic inclusions. Neuroinflammation associated with microglial cells is typically located in brain regions with α-syn deposits. The potential link between microglial cell migration and the transport of pathological α-syn protein in MSA was investigated. Qualitative analysis via immunofluorescence of MSA cases (n = 4) revealed microglial cells bearing α-syn inclusions distal from oligodendrocytes bearing α-syn cytoplasmic inclusions, as well as close interactions between microglia and oligodendrocytes bearing α-syn, suggestive of a potential transfer mechanism between microglia and α-syn bearing cells in MSA and the possibility of microglia acting as a mobile vehicle to spread α-syn between anatomically connected brain regions...
April 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29673550/complex-role-of-chemokine-mediators-in-animal-models-of-alzheimer-s-disease
#19
REVIEW
Elodie Martin, Cécile Delarasse
Chemokines are a family of cytokines, first described to play a role in the immune system. However, neurons and glial cells also express chemokines and their receptors. In the central nervous system, chemokines are involved in several neural functions, in particular in the control of cell communications and neuronal activity. In pathological conditions, chemokines participate in neuroinflammatory and neurodegenerative processes. In Alzheimer's disease (AD), chemokines play a role in the development of the two main lesions, amyloid β plaques and neurofibrillary tangles...
February 2018: Biomedical Journal
https://www.readbyqxmd.com/read/29673549/tau-and-neuroinflammation-what-impact-for-alzheimer-s-disease-and-tauopathies
#20
REVIEW
Cyril Laurent, Luc Buée, David Blum
Alzheimer's Disease (AD) is a chronic neurodegenerative disorder and the most common type of dementia (60-80% of cases). In 2016, nearly 44 million people were affected by AD or related dementia. AD is characterized by progressive neuronal damages leading to subtle and latter obvious decline in cognitive functions including symptoms such as memory loss or confusion, which ultimately require full-time medical care. Its neuropathology is defined by the extracellular accumulation of amyloid-β (Aβ) peptide into amyloid plaques, and intraneuronal neurofibrillary tangles (NFT) consisting of aggregated hyper- and abnormal phosphorylation of tau protein...
February 2018: Biomedical Journal
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