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Neurodegenerative diseases

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https://www.readbyqxmd.com/read/29777961/non-viral-delivery-of-an-optogenetic-tool-into-cells-with-self-healing-hydrogel
#1
Fu-Yu Hsieh, Hao-Wei Han, Xiao-Ru Chen, Chii-Shen Yang, Yen Wei, Shan-Hui Hsu
Optogenetics offers unique, temporally precise control of neural activity in genetically targeted specific neurons that express light-sensitive opsin molecules. Three-dimensional (3D) delivery of optogenetics can be realized by co-injection of bacteriorhodopsin (HEBR) plasmid with a chitosan-based self-healing hydrogel with strong shear-thinning properties. The HEBR protein shows photoelectrical properties and can be used as an optical switch for cell activation. We optimize the shear force generated during the process of injection (∼100 Pa), which is transient because of the self-healing nature of the hydrogel...
May 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29777754/hmgb1-neutralization-attenuates-hippocampal-neuronal-death-and-cognitive-impairment-in-rats-with-chronic-cerebral-hypoperfusion-via-suppressing-inflammatory-responses-and-oxidative-stress
#2
Yue Hei, Rong Chen, Xicai Yi, Qianfa Long, Dakuan Gao, Weiping Liu
High mobility group box-1 (HMGB1) acts as a proinflammatory molecule once released into the extracellular space and inhibition of HMGB1 signaling has been reported be neuroprotective in neurodegenerative diseases. Besides, chronic cerebral hypoperfusion (CCH) causes cognitive impairment in neurodegenerative diseases. Here we tested the protective role of HMGB1 inhibition using anti-HMGB1 neutralizing antibody (Ab) against CCH in rats after bilateral common carotid artery occlusion (2VO). 169 male Sprague-Dawley rats underwent 2VO or sham operation...
May 16, 2018: Neuroscience
https://www.readbyqxmd.com/read/29777524/mercury-involvement-in-neuronal-damage-and-in-neurodegenerative-diseases
#3
REVIEW
Veronica Lanza Cariccio, Annalisa Samà, Placido Bramanti, Emanuela Mazzon
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis are characterized by a chronic and selective process of neuronal cell death. Although the causes of neurodegenerative diseases remain still unknown, it is now a well-established idea that more factors, such as genetic, endogenous, and environmental, are involved. Among environmental causes, the accumulation of mercury, a heavy metal considered a toxic agent, was largely studied as a probable factor involved in neurodegenerative disease course...
May 18, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29777184/genotype-phenotype-links-in-frontotemporal-lobar-degeneration
#4
REVIEW
Sara Van Mossevelde, Sebastiaan Engelborghs, Julie van der Zee, Christine Van Broeckhoven
Frontotemporal lobar degeneration (FTLD) represents a group of neurodegenerative brain diseases with highly heterogeneous clinical, neuropathological and genetic characteristics. This high degree of heterogeneity results from the presence of several different underlying molecular disease processes; consequently, it is unlikely that all patients with FTLD will benefit from a single therapy. Therapeutic strategies for FTLD are currently being explored, and tools are urgently needed that enable the selection of patients who are the most likely to benefit from a particular therapy...
May 18, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29777037/inhibition-of-tbc1d5-activates-rab7a-and-can-enhance-the-function-of-the-retromer-cargo-selective-complex
#5
Matthew N J Seaman, Aamir S Mukadam, Sophia Y Breusegem
The retromer complex is a vital component of the endosomal protein sorting machinery being necessary for sorting into both the endosome-to-Golgi retrieval pathway and also the endosome-to-cell-surface recycling pathway. Retromer mediates cargo selection through a trimeric complex comprising VPS35, VPS29 and VPS26 which is recruited to endosomes by binding to Rab7a and Snx3. Retromer function is linked to two distinct neurodegenerative diseases, Parkinson's disease and Alzheimer's disease and modulating retromer function has been proposed as an avenue to explore for a putative therapy in these conditions...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29776894/amyloid-pet-in-neurodegenerative-diseases-with-dementia
#6
V Camacho, A Gómez-Grande, P Sopena, D García-Solís, M Gómez Río, C Lorenzo, S Rubí, J Arbizu
Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI)...
May 15, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/29776378/differential-induction-of-mutant-sod1-misfolding-and-aggregation-by-tau-and-%C3%AE-synuclein-pathology
#7
Michael C Pace, Guilian Xu, Susan Fromholt, John Howard, Benoit I Giasson, Jada Lewis, David R Borchelt
BACKGROUND: Prior studies in C. elegans demonstrated that the expression of aggregation-prone polyglutamine proteins in muscle wall cells compromised the folding of co-expressed temperature-sensitive proteins, prompting interest in whether the accumulation of a misfolded protein in pathologic features of human neurodegenerative disease burdens cellular proteostatic machinery in a manner that impairs the folding of other cellular proteins. METHODS: Mice expressing high levels of mutant forms of tau and α-synuclein (αSyn), which develop inclusion pathologies of the mutant protein in brain and spinal cord, were crossed to mice expressing low levels of mutant superoxide dismutase 1 fused to yellow fluorescent protein (G85R-SOD1:YFP) for aging and neuropathological evaluation...
May 18, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29776328/recent-progress-and-considerations-for-aav-gene-therapies-targeting-the-central-nervous-system
#8
REVIEW
Erik Allen Lykken, Charles Shyng, Reginald James Edwards, Alejandra Rozenberg, Steven James Gray
BACKGROUND: Neurodevelopmental disorders, as a class of diseases, have been particularly difficult to treat even when the underlying cause(s), such as genetic alterations, are understood. What treatments do exist are generally not curative and instead seek to improve quality of life for affected individuals. The advent of gene therapy via gene replacement offers the potential for transformative therapies to slow or even stop disease progression for current patients and perhaps minimize or prevent the appearance of symptoms in future patients...
May 18, 2018: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/29776014/association-of-objectively-measured-physical-activity-with-brain-structure-uk-biobank-study
#9
Mark Hamer, Nikhil Sharma, G David Batty
BACKGROUND: Physical activity may be beneficial for cognition but mechanisms are unclear. We examined the association between objectively assessed physical activity and brain volume, with a focus on the hippocampus region. METHODS: We used data from UK Biobank (n=5,272; aged 55.4±7.5 yrs; 45.6% men) collected through 2013-2016. Participants wore the Axivity AX3 wrist-worn triaxial accelerometer for seven days to assess habitual physical activity. Structural magnetic resonance imaging was performed using a standard Siemens Skyra 3T running VD13A SP4 to obtain images of the brain...
May 18, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29775961/antioxidant-response-elements-discovery-classes-regulation-and-potential-applications
#10
REVIEW
Azhwar Raghunath, Kiruthika Sundarraj, Raju Nagarajan, Frank Arfuso, Jinsong Bian, Alan P Kumar, Gautam Sethi, Ekambaram Perumal
Exposure to antioxidants and xenobiotics triggers the expression of a myriad of genes encoding antioxidant proteins, detoxifying enzymes, and xenobiotic transporters to offer protection against oxidative stress. This articulated universal mechanism is regulated through the cis-acting elements in an array of Nrf2 target genes called antioxidant response elements (AREs), which play a critical role in redox homeostasis. Though the Keap1/Nrf2/ARE system involves many players, AREs hold the key in transcriptional regulation of cytoprotective genes...
May 7, 2018: Redox Biology
https://www.readbyqxmd.com/read/29775624/characterization-and-comparative-analysis-of-a-new-mouse-microglial-cell-model-for-studying-neuroinflammatory-mechanisms-during-neurotoxic-insults
#11
Souvarish Sarkar, Emir Malovic, Deeksha Sarda, Vivek Lawana, Dharmin Rokad, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Microglia are the first responders of the central nervous system, acting as the key modulators of neuroinflammation observed during neurotoxic insults as well as in the pathophysiology of several neurodegenerative disorders including Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD). The number of publications on microglia has increased steadily throughout the past decade because of immense interests in the neuroinflammation that precedes the neurodegenerative process. To study microglial biology and its role in modulating neuroinflammation, immortalized microglial cell lines derived from mice, rats, and humans have been developed...
May 15, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29775591/disease-associated-microglia-a-universal-immune-sensor-of-neurodegeneration
#12
REVIEW
Aleksandra Deczkowska, Hadas Keren-Shaul, Assaf Weiner, Marco Colonna, Michal Schwartz, Ido Amit
A major challenge in the field of neurodegenerative diseases and brain aging is to identify the body's intrinsic mechanism that could sense the central nervous system (CNS) damage early and protect the brain from neurodegeneration. Accumulating evidence suggests that disease-associated microglia (DAM), a recently identified subset of CNS resident macrophages found at sites of neurodegeneration, might play such a protective role. Here, we propose that microglia are endowed with a dedicated sensory mechanism, which includes the Trem2 signaling pathway, to detect damage within the CNS in the form of neurodegeneration-associated molecular patterns (NAMPs)...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29775304/sesquiterpenoids-from-chloranthus-anhuiensis-with-neuroprotective-effects-in-pc12-cells
#13
Jian Xu, Hui-Lin Zhu, Jie Zhang, Tao Du, Er-Yan Guo, Wen-Yuan Liu, Jian-Guang Luo, Feng Ye, Feng Feng, Wei Qu
Glutamate-induced excitotoxicity plays a vital role in neurodegenerative diseases. Neuroprotection against excitotoxicity has been considered as an effective experimental approach for preventing and/or treating excitotoxicity-mediated diseases. In the present study, six new sesquiterpenoids (1-6) and 26 known compounds of this type (7-32) were isolated and characterized from the whole plants of Chloranthus anhuiensis. Chlorantolide A (1) is the first example of a 5,6- seco-germacrane-type sesquiterpenoid, while phacadinane E (2) is a rare 4,5- seco-cadinane-type sesquiterpenoid...
May 18, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29775216/neuroimmflammation-and-microglia-in-glaucoma-time-for-a-paradigm-shift
#14
REVIEW
Xin Wei, Kin-Sang Cho, Eric F Thee, Martine J Jager, Dong Feng Chen
Glaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i...
May 18, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29775139/burden-and-strain-among-familial-caregivers-of-patients-with-dementia-in-china
#15
Min Zhang, Yu-Ping Chang, Yu Jin Liu, Ling Gao, Davina Porock
BACKGROUND: Alzheimer's disease is one of a variety of progressive and ultimately fatal neurodegenerative diseases that are characterized by a number of nervous and mental symptoms and behavior disorders. These problems are likely to cause burden and strain on caregivers. In this study, we demonstrated the level and relationship of burden and strain among caregivers of dementia patients in China. METHODS: A total of 212 caregivers of family members with dementia responded to the survey...
May 2018: Issues in Mental Health Nursing
https://www.readbyqxmd.com/read/29774890/genetic-and-clinical-aspects-of-wolfram-syndrome-1-a-severe-neurodegenerative-disease
#16
REVIEW
Luciana Rigoli, Placido Bramanti, Chiara Di Bella, Filippo De Luca
Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and other abnormalities. WS1 usually results in death before the age of 50 years. The pathogenesis of WS1 is ascribed to mutations of human WFS1 gene on chromosome 4p encoding a transmembrane protein called wolframin which has physiological functions in membrane trafficking, secretion, processing, and/or regulation of ER calcium homeostasis. Different types of WFS1 mutations have been identified, and some of these have been associated with a dominant, severe type of WS...
May 2018: Pediatric Research
https://www.readbyqxmd.com/read/29774231/semaphorin3a-signaling-is-dispensable-for-motor-axon-reinnervation-of-the-adult-neuromuscular-junction
#17
Jennifer L Shadrach, Brian A Pierchala
The neuromuscular junction (NMJ) is a specialized synapse that is formed by motor axon innervation of skeletal muscle fibers. The maintenance of motor-muscle connectivity is critical for the preservation of muscle tone and generation of movement. Injury can induce a robust regenerative response in motor axons, but severe trauma or chronic denervation resulting from neurodegenerative disease typically leads to inefficient repair and poor functional recovery. The axon guidance molecule Semaphorin3A (Sema3A) has been implicated as a negative regulator of motor innervation...
May 2018: ENeuro
https://www.readbyqxmd.com/read/29773988/microglia-p2y-13-receptors-prevent-astrocyte-proliferation-mediated-by-p2y-1-receptors
#18
Clara Quintas, Nuno Vale, Jorge Gonçalves, Glória Queiroz
Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773975/cold-shock-induced-protein-rbm3-but-not-mild-hypothermia-protects-human-sh-sy5y-neuroblastoma-cells-from-mpp-induced-neurotoxicity
#19
Hai-Jie Yang, Xiang Shi, Fei Ju, Bei-Ning Hao, Shuang-Ping Ma, Lei Wang, Bin-Feng Cheng, Mian Wang
The cold shock protein RBM3 can mediate mild hypothermia-related protection in neurodegeneration such as Alzheimer's disease. However, it remains unclear whether RBM3 and mild hypothermia provide same protection in model of Parkinson's disease (PD), the second most common neurodegenerative disorder. In this study, human SH-SY5Y neuroblastoma cells subjected to insult by 1-methyl-4-phenylpyridinium (MPP+ ) served as an in-vitro model of PD. Mild hypothermia (32°C) aggravated MPP+ -induced apoptosis, which was boosted when RBM3 was silenced by siRNA...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29773347/lipophilic-methylene-blue-analogues-enhance-mitochondrial-function-and-increase-frataxin-levels-in-a-cellular-model-of-friedreich-s-ataxia
#20
Omar M Khdour, Indrajit Bandyopadhyay, Sandipan Roy Chowdhury, Nishant P Visavadiya, Sidney M Hecht
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder resulting from reduced expression of the protein frataxin (FXN). Although its function is not fully understood, frataxin appears to help assemble iron sulfur clusters; these are critical for the function of many proteins, including those needed for mitochondrial energy production. Finding ways to increase FXN levels has been a major therapeutic strategy for this disease. Previously, we described a novel series of methylene violet analogues and their structural optimization as potential therapeutic agents for neurodegenerative and mitochondrial disorders...
May 4, 2018: Bioorganic & Medicinal Chemistry
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