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https://www.readbyqxmd.com/read/28930518/microperimetric-biofeedback-training-fundamentals-strategies-and-perspectives
#1
Enzo Maria Vingolo, Giuseppe Napolitano, Serena Fragiotta
Microperimetric biofeedback training (MBFT) is a visual rehabilitative strategy based on fixation stability improvement reinforcing or creating a new preferential fixation locus. The rationale consists in reeducating visual system to a new visual condition, promoting retina-brain transmission, and thus cortical plasticity. The use of MBFT found is major application in visual diseases involving central vision, but later it revealed promising functional outcomes even in myopia, inherited retinal degenerations and nystagmus...
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
#2
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/28929132/interplay-between-protein-glycosylation-pathways-in-alzheimer-s-disease
#3
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/28928740/microbiome-derived-lipopolysaccharide-enriched-in-the-perinuclear-region-of-alzheimer-s-disease-brain
#4
Yuhai Zhao, Lin Cong, Vivian Jaber, Walter J Lukiw
Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years of intense study, the origin and molecular mechanics of these AD-relevant pathogenic signals are still not well understood. Here, we provide evidence that an intensely pro-inflammatory bacterial lipopolysaccharide (LPS), part of a complex mixture of pro-inflammatory neurotoxins arising from abundant Gram-negative bacilli of the human gastrointestinal (GI) tract, are abundant in AD-affected brain neocortex and hippocampus...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928628/axonal-degeneration-during-aging-and-its-functional-role-in-neurodegenerative-disorders
#5
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/28926781/a-leukomyeloencephalopathy-of-unknown-origin-in-an-azawakh-dog
#6
Maria Teresa Mandara, Alice Reginato, Federica Balducci, Marco Bernardini
A diffuse bilaterally symmetrical leukomyeloencephalopathy was observed in a 6-year-old male Azawakh dog showing a slowly progressive ataxia of six months duration associated with sensory disorders. Severe bilaterally symmetrical demyelination and vacuolisation were confined to the dorsal columns along the entire spinal cord with a minor axonal degeneration. The main changes of myelin sheaths consisted in splitting and intramyelin vacuolization. Naked axons were scattered in a network of astrocytic processes and collagen fibres...
September 5, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28926646/vascular-hypoperfusion-in-acute-optic-neuritis-is-a-potentially-new-neurovascular-model-for-demyelinating-diseases
#7
Ta-Ching Chen, Chao-Yuan Yeh, Chao-Wen Lin, Chung-May Yang, Chang-Hao Yang, I-Hung Lin, Pao-Yang Chen, Jung-Yu Cheng, Fung-Rong Hu
PURPOSE: Optic neuritis is highly correlated with multiple sclerosis and is a major cause of acute visual loss and long-term neuronal degeneration. Primary cerebral hypoperfusion has been reported in brain demyelinating diseases. This study investigated whether peripapillary perfusion is changed in patients with acute optic neuritis (AON). METHODS: This three-year cohort study was conducted from September 1 2012, to August 31, 2015. Two hundred and forty-one patients with non-glaucomatous acute optic neuropathy were screened, and 42 non-highly myopic patients who had suffered their first episode of unilaterally idiopathic AON were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28923480/impact-of-morphine-on-the-expression-of-insulin-receptor-and-protein-levels-of-insulin-igfs-in-rat-neural-stem-cells
#8
Sadegh Salarinasab, AliReza Nourazarian, Masoud Nikanfar, Nima Abdyazdani, Masoumeh Kazemi, Navid Feizy, Reza Rahbarghazi
Alzheimer's disease is correlated with neuronal degeneration and loss of neuronal precursors in different parts of the brain. It has been found disturbance in the homeostasis neural stem cells (NSCs) can cause neurodegeneration. Morphine, an analgesic agent, can disrupt the dynamic and normal state of NSCs. However, more investigations are required to clearly address underlying mechanisms. The current experiment aimed to investigate the effects of morphine on the cell distribution of insulin factor and receptor and insulin-like growth factors (IGF1, IGF2) in NSCs...
September 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28918510/acquired-hepatocerebral-degeneration-ahd-a-peculiar-neurological-impairment-in-advanced-chronic-liver-disease
#9
A Pigoni, F Iuculano, C Saetti, L Airaghi, L Burdick, S Spreafico, M Curioni, R Lombardi, L Valenti, A L Fracanzani, S Fargion
We discuss the case of a rare and often unrecognized neurologic syndrome, called Acquired Hepatocerebral Degeneration (AHD), observed in patients with advanced liver disease and portosystemic shunts. The clinical manifestations can be very heterogeneous and in our case included a combination of cerebellar and extrapyramidal signs, arisen in a period of few days. Brain Magnetic Resonance Imaging (MRI) showed, in T1-weighted images, diffuse bilateral hyper intensities in basal ganglia and biemispheric brain and cerebellar cortices, resembling paramagnetic deposits...
September 16, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28918258/olfactory-function-in-an-excitotoxic-model-for-secondary-neuronal-degeneration-role-of-dopaminergic-interneurons
#10
Concepció Marin, Sara Laxe, Cristobal Langdon, Joan Berenguer, Eduardo Lehrer, Franklin Mariño-Sánchez, Isam Alobid, Montserrat Bernabeu, Joaquim Mullol
Secondary neuronal degeneration (SND) occurring in Traumatic brain injury (TBI) consists in downstream destructive events affecting cells that were not or only marginally affected by the initial wound, further increasing the effects of the primary injury. Glutamate excitotoxicity is hypothesized to play an important role in SND. TBI is a common cause of olfactory dysfunction that may be spontaneous and partially recovered. The role of the glutamate excitotoxicity in the TBI-induced olfactory dysfunction is still unknown...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28916769/therapeutic-effects-of-the-mitochondrial-ros-redox-modulator-kh176-in-a-mammalian-model-of-leigh-disease
#11
Ria de Haas, Devashish Das, Alejandro Garanto, Herma G Renkema, Rick Greupink, Petra van den Broek, Jeanne Pertijs, Rob W J Collin, Peter Willems, Julien Beyrath, Arend Heerschap, Frans G Russel, Jan A Smeitink
Leigh Disease is a progressive neurometabolic disorder for which a clinical effective treatment is currently still lacking. Here, we report on the therapeutic efficacy of KH176, a new chemical entity derivative of Trolox, in Ndufs4 (-/-) mice, a mammalian model for Leigh Disease. Using in vivo brain diffusion tensor imaging, we show a loss of brain microstructural coherence in Ndufs4 (-/-) mice in the cerebral cortex, external capsule and cerebral peduncle. These findings are in line with the white matter diffusivity changes described in mitochondrial disease patients...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916178/the-cerebellum-s-contribution-to-beat-interval-discrimination
#12
S Paquette, S Fujii, H C Li, G Schlaug
From expert percussionists to individuals who cannot dance, there are widespread differences in people's abilities to perceive and synchronize with a musical beat. The aim of our study was to identify candidate brain regions that might be associated with these abilities. For this purpose, we used Voxel-Based-Morphometry to correlate inter-individual differences in performance on the Harvard Beat Assessment Tests (H-BAT) with local inter-individual variations in gray matter volumes across the entire brain space in 60 individuals...
September 12, 2017: NeuroImage
https://www.readbyqxmd.com/read/28915852/a-novel-frameshift-grn-mutation-results-in-frontotemporal-lobar-degeneration-with-a-distinct-clinical-phenotype-in-two-siblings-case-report-and-literature-review
#13
Takashi Hosaka, Kazuhiro Ishii, Takeshi Miura, Naomi Mezaki, Kensaku Kasuga, Takeshi Ikeuchi, Akira Tamaoka
BACKGROUND: Progranulin gene (GRN) mutations are major causes of frontotemporal lobar degeneration. To date, 68 pathogenic GRN mutations have been identified. However, very few of these mutations have been reported in Asians. Moreover, some GRN mutations manifest with familial phenotypic heterogeneity. Here, we present a novel GRN mutation resulting in frontotemporal lobar degeneration with a distinct clinical phenotype, and we review reports of GRN mutations associated with familial phenotypic heterogeneity...
September 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28914737/evidence-of-semantic-processing-impairments-in-behavioural-variant-frontotemporal-dementia-and-parkinson-s-disease
#14
Katheryn A Q Cousins, Murray Grossman
PURPOSE OF REVIEW: Category-specific impairments caused by brain damage can provide important insights into how semantic concepts are organized in the brain. Recent research has demonstrated that disease to sensory and motor cortices can impair perceptual feature knowledge important to the representation of semantic concepts. This evidence supports the grounded cognition theory of semantics, the view that lexical knowledge is partially grounded in perceptual experience and that sensory and motor regions support semantic representations...
September 13, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28912300/-18-f-av-1451-binding-in-vivo-mirrors-the-expected-distribution-of-tdp-43-pathology-in-the-semantic-variant-of-primary-progressive-aphasia
#15
W R Bevan-Jones, Thomas E Cope, P Simon Jones, Luca Passamonti, Young T Hong, Tim D Fryer, Robert Arnold, Kieren S J Allinson, Jonathan P Coles, Franklin I Aigbirhio, Karalyn Patterson, John T O'Brien, James B Rowe
INTRODUCTION: Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [(18)F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. METHODS AND RESULTS: Seven patients (five with svPPA and two with 'right' semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [(18)F]AV-1451...
September 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28903492/editor-s-highlight-nlrp3-is-required-for-inflammatory-changes-and-nigral-cell-loss-resulting-from-chronic-intragastric-rotenone-exposure-in-mice
#16
Eileen M Martinez, Alison L Young, Yash R Patankar, Brent L Berwin, Li Wang, Katharine M von Herrmann, Jaclyn M Weier, Matthew C Havrda
Complex interactions between genetic and environmental factors are widely believed to underlie the incidence and progression of Parkinson's disease (PD). Rotenone is a naturally occurring metabolic toxin employed as an insecticide and piscicide identified as a risk factor for the development of PD in agricultural workers. The Nlrp3 inflammasome is an intracellular mediator that can initiate an inflammatory cascade in response to cellular stress. Reports by others indicating that NLRP3 expression was detectable in tissues obtained from Alzheimer's disease patients and that the PD-associated protein α-synuclein could activate inflammasomes in cultured glial cells, prompted us to test the prediction that Nlrp3 was required for the development of Parkinson's-like changes resulting from rotenone exposure in mice...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903038/lipidomic-and-transcriptomic-basis-of-lysosomal-dysfunction-in-progranulin-deficiency
#17
Bret M Evers, Carlos Rodriguez-Navas, Rachel J Tesla, Janine Prange-Kiel, Catherine R Wasser, Kyoung Shin Yoo, Jeffrey McDonald, Basar Cenik, Thomas A Ravenscroft, Florian Plattner, Rosa Rademakers, Gang Yu, Charles L White, Joachim Herz
Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL) and Niemann-Pick type C (NPC), and is implicated in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD-TDP) with progranulin (PGRN) deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Using an unbiased lipidomic approach, we found that brain lipid composition in humans and mice with PGRN deficiency shows disease-specific differences that distinguish them from normal and other pathologic groups...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28901458/neuroprotective-effects-of-curcumin-alleviate-lumbar-intervertebral-disc-degeneration-through-regulating-the-expression-of-inos-cox%C3%A2-2-tgf%C3%A2-%C3%AE-1-2-mmp%C3%A2-9-and-bdnf-in-a-rat-model
#18
Yuan Hu, Jin-Shu Tang, Shu-Xun Hou, Xiu-Xiu Shi, Jiang Qin, Tie-Song Zhang, Xiao-Jing Wang
Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900183/a-brain-derived-neurotrophic-factor-mimetic-is-sufficient-to-restore-cone-photoreceptor-visual-function-in-an-inherited-blindness-model
#19
Conor Daly, Lisa Shine, Theresa Heffernan, Sudhakar Deeti, Alison L Reynolds, John J O'Connor, Eugène T Dillon, David J Duffy, Walter Kolch, Gerard Cagney, Breandán N Kennedy
Controversially, histone deacetylase inhibitors (HDACi) are in clinical trial for the treatment of inherited retinal degeneration. Utilizing the zebrafish dye (ucd6) model, we determined if treatment with HDACi can rescue cone photoreceptor-mediated visual function. dye exhibit defective visual behaviour and retinal morphology including ciliary marginal zone (CMZ) cell death and decreased photoreceptor outer segment (OS) length, as well as gross morphological defects including hypopigmentation and pericardial oedema...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900002/modeling-parkinson-s-disease-pathology-by-combination-of-fibril-seeds-and-%C3%AE-synuclein-overexpression-in-the-rat-brain
#20
Poonam Thakur, Ludivine S Breger, Martin Lundblad, Oi Wan Wan, Bengt Mattsson, Kelvin C Luk, Virginia M Y Lee, John Q Trojanowski, Anders Björklund
Although a causative role of α-synuclein (α-syn) is well established in Parkinson's disease pathogenesis, available animal models of synucleinopathy do not replicate the full range of cellular and behavioral changes characteristic of the human disease. This study was designed to generate a more faithful model of Parkinson's disease by injecting human α-syn fibril seeds into the rat substantia nigra (SN), in combination with adenoassociated virus (AAV)-mediated overexpression of human α-syn, at levels that, by themselves, are unable to induce acute dopamine (DA) neurodegeneration...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
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