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Neurodegenerative diseases

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https://www.readbyqxmd.com/read/28735170/effects-of-different-solvents-on-the-conformations-of-apoptotic-cytochrome-c-structural-insights-from-molecular-dynamics-simulation
#1
Gurusamy Muneeswaran, Subramanian Kartheeswaran, Kaliappan Muthukumar, Christopher D Dharmaraj, Chandran Karunakaran
Cytochrome c (cyt-c) upon binding with cardiolipin acquires peroxidase activity and is strictly connected to the pathogenesis of many human diseases including neurodegenerative and cardiovascular diseases. Interaction of cyt-c with cardiolipin mimics partial unfolding/conformational changes of cyt-c in different solvent environments. Dynamic pictures of these conformational changes of cyt-c are crucial in understanding their physiological roles in mitochondrial functions. Therefore, atomistic molecular dynamics (MD) simulations have been carried out to investigate the effect of different solvents (water, urea/water, MeOH and DMSO) on the structure and conformations of apoptotic cyt-c (Fe(3+))...
July 14, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28735012/fgwas-functional-genome-wide-association-analysis
#2
Chao Huang, Paul Thompson, Yalin Wang, Yang Yu, Jingwen Zhang, Dehan Kong, Rivka R Colen, Rebecca C Knickmeyer, Hongtu Zhu
Functional phenotypes (e.g., subcortical surface representation), which commonly arise in imaging genetic studies, have been used to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. However, existing statistical methods largely ignore the functional features (e.g., functional smoothness and correlation). The aim of this paper is to develop a functional genome-wide association analysis (FGWAS) framework to efficiently carry out whole-genome analyses of functional phenotypes...
July 19, 2017: NeuroImage
https://www.readbyqxmd.com/read/28734548/ubiquitin-like-modifications-in-the-dna-damage-response
#3
REVIEW
Zhifeng Wang, Wei-Guo Zhu, Xingzhi Xu
Genomic DNA is damaged at an extremely high frequency by both endogenous and environmental factors. An improper response to DNA damage can lead to genome instability, accelerate the aging process and ultimately cause various human diseases, including cancers and neurodegenerative disorders. The mechanisms that underlie the cellular DNA damage response (DDR) are complex and are regulated at many levels, including at the level of post-translational modification (PTM). Since the discovery of ubiquitin in 1975 and ubiquitylation as a form of PTM in the early 1980s, a number of ubiquitin-like modifiers (UBLs) have been identified, including small ubiquitin-like modifiers (SUMOs), neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), interferon-stimulated gene 15 (ISG15), human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10), ubiquitin-fold modifier 1 (UFRM1), URM1 ubiquitin-related modifier-1 (URM1), autophagy-related protein 12 (ATG12), autophagy-related protein 8 (ATG8), fan ubiquitin-like protein 1 (FUB1) and histone mono-ubiquitylation 1 (HUB1)...
July 11, 2017: Mutation Research
https://www.readbyqxmd.com/read/28734388/axonal-transport-dysfunction-in-neurodegenerative-diseases-the-holy-grail-for-developing-disease-modifying-therapies
#4
EDITORIAL
Jennifer T Lamberts, Patrik Brundin
No abstract text is available yet for this article.
September 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28733961/a-review-of-biomarkers-for-neurodegenerative-disease-will-they-swing-us-across-the-valley
#5
REVIEW
Thomas G Beach
Measures of the severity of cognitive impairment or parkinsonism are the usual endpoints in clinical trials for Alzheimer's disease (AD) and Parkinson's disease (PD), but are critically hampered by their lack of disease sensitivity and specificity. Due to the high failure rate of clinical trials, the rate of regulatory approval for efficacious new drugs has stagnated in the past few decades, with the gap between basic science discovery and clinical application metaphorically termed the "Valley of Death". While the causes for this are probably multiple and complex, the usage of biomarkers as surrogate endpoints, particularly when they are molecularly-specific for the disease, has achieved some success in cancer trials, and it is likely that neurodegenerative disease trials would benefit from the same approach...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#6
Hani S Hafez, Doaa A Ghareeb, Samar R Saleh, Mariam M Abady, Maha A El Demellawy, Hend Hussien, Nihad Abdel-Monem
BACKGROUND: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28733489/interaction-of-misfolded-proteins-and-mitochondria-in-neurodegenerative-disorders
#7
REVIEW
Andrey Y Abramov, Alexey V Berezhnov, Evgeniya I Fedotova, Valery P Zinchenko, Ludmila P Dolgacheva
The number of the people affected by neurodegenerative disorders is growing dramatically due to the ageing of population. The major neurodegenerative diseases share some common pathological features including the involvement of mitochondria in the mechanism of pathology and misfolding and the accumulation of abnormally aggregated proteins. Neurotoxicity of aggregated β-amyloid, tau, α-synuclein and huntingtin is linked to the effects of these proteins on mitochondria. All these misfolded aggregates affect mitochondrial energy metabolism by inhibiting diverse mitochondrial complexes and limit ATP availability in neurones...
July 21, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28733362/loss-of-cln5-causes-altered-neurogenesis-in-a-childhood-neurodegenerative-disorder
#8
E Savchenko, Y Singh, H Konttinen, K Lejavova, L Mediavilla Santos, A Grubman, V Kärkkäinen, V Keksa-Goldsteine, N Naumenko, P Tavi, A R White, T M Malm, J Koistinaho, K M Kanninen
Neural stem/progenitor cells (NPCs) generate new neurons in the brain throughout the lifetime in an intricate process called neurogenesis. Neurogenic alterations are a common feature of several adult-onset neurodegenerative diseases. The neuronal ceroid lipofuscinoses (NCLs) are the most common group of inherited neurodegenerative diseases that mainly affect children. Pathological features of the NCLs include accumulation of lysosomal storage material, neuroinflammation, and neuronal degeneration, yet the exact cause of this group of diseases remains poorly understood...
July 21, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28733218/esculentoside-a-inhibits-lps-induced-bv2-microglia-activation-through-activating-ppar-%C3%AE
#9
Dong Li-Hua, Li Yan, Wang Shi-Ji, Wang Guang, Sheng Lu-Lu, Pan Xue-Feng, Sun Pengda
Neuroinflammation has been recognized as a factor in the pathogenesis of neurodegenerative diseases. Esculentoside A (EsA), a saponin isolated from Phytolacca esculenta, has been reported to have anti-inflammatory activity. However, little research has been reported on the anti-neuroinflammatory effects of EsA. EsA concentration-dependently suppressed LPS-induced TNF-α, IL-1β, and PGE2 production. LPS-induced NF-κB activation was inhibited by treatment of EsA. Furthermore, EsA concentration-dependently up-regulated the expression of PPAR-γ...
July 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28733129/endocannabinoids-exert-cb1-receptor-mediated-neuroprotective-effects-in-models-of-neuronal-damage-induced-by-hiv-1-tat-protein
#10
Changqing Xu, Douglas J Hermes, Blessing Nwanguma, Ian R Jacobs, Kenneth Mackie, Somnath Mukhopadhyay, Aron H Lichtman, Bogna Ignatowska-Jankowska, Sylvia Fitting
In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids (eCBs) elicit neuroprotective and anti-inflammatory actions in several central nervous system (CNS) disease models, but their effects in HAND remain unknown. HIV-1 does not infect neurons, but produces viral toxins, such as transactivator of transcription (Tat), that disrupt neuronal calcium equilibrium and give rise to synaptodendritic injuries and cell death, the former being highly correlated with HAND...
July 18, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28731859/air-pollution-and-parkinson-s-disease-evidence-and-future-directions
#11
REVIEW
Natalia Palacios
Parkinson's disease (PD) is a neurodegenerative disease of unknown etiology that is thought to be caused by a complex combination of environmental and/or genetic factors. Air pollution exposure is linked to numerous adverse effects on human health, including brain inflammation and oxidative stress, processes that are believed to contribute to the development and progression of PD. This review provides an overview of recent advances in the epidemiology of air pollution and PD, including evidence of the effects of various pollutants (ozone, PM10, PM2...
July 21, 2017: Reviews on Environmental Health
https://www.readbyqxmd.com/read/28731838/neuroprotection-in-glaucoma-animal-models-and-clinical-trials
#12
Mohammadali Almasieh, Leonard A Levin
Glaucoma is a progressive neurodegenerative disease that frequently results in irreversible blindness. Glaucoma causes death of retinal ganglion cells (RGCs) and their axons in the optic nerve, resulting in visual field deficits and eventual loss of visual acuity. Glaucoma is a complex optic neuropathy, and a successful strategy for its treatment requires not only better management of known risk factors such as elevated intraocular pressure and the development of improved tools for detecting RGC injury but also treatments that address this injury (i...
July 21, 2017: Annual Review of Vision Science
https://www.readbyqxmd.com/read/28731570/susceptibility-weighted-imaging-and-quantitative-susceptibility-mapping-of-the-cerebral-vasculature-using-ferumoxytol
#13
Saifeng Liu, Jean-Christophe Brisset, Jiani Hu, E Mark Haacke, Yulin Ge
PURPOSE: To demonstrate the potential of imaging cerebral arteries and veins with ferumoxytol using susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: The relationships between ferumoxytol concentration and the apparent susceptibility at 1.5T, 3T, and 7T were determined using phantom data; the ability of visualizing subvoxel vessels was evaluated using simulations; and the feasibility of using ferumoxytol to enhance the visibility of small vessels was confirmed in three healthy volunteers at 7T(with doses 1 mg/kg to 4 mg/kg)...
July 21, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28731449/cerebrospinal-fluid-neurogranin-as-a-biomarker-of-neurodegenerative-diseases-a-cross-sectional-study
#14
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Robert Nisticò, Roberto Floris, Francesco Garaci, Harald Hampel
We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35), FTD (n = 9), MCI (n = 41), cognitively HC (n = 23)]...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731444/the-relationship-of-brain-amyloid-load-and-apoe-status-to-regional-cortical-thinning-and-cognition-in-the-adni-cohort
#15
Chunfei Li, David A Loewenstein, Ranjan Duara, Mercedes Cabrerizo, Warren Barker, Malek Adjouadi
BACKGROUND: Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment. OBJECTIVE: To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4-), Aβ status (Amy+∖Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731442/of-mice-and-men-comparative-analysis-of-neuro-inflammatory-mechanisms-in-human-and-mouse-using-cause-and-effect-models
#16
Alpha Tom Kodamullil, Anandhi Iyappan, Reagon Karki, Sumit Madan, Erfan Younesi, Martin Hofmann-Apitius
Perturbance in inflammatory pathways have been identified as one of the major factors which leads to neurodegenerative diseases (NDD). Owing to the limited access of human brain tissues and the immense complexity of the brain, animal models, specifically mouse models, play a key role in advancing the NDD field. However, many of these mouse models fail to reproduce the clinical manifestations and end points of the disease. NDD drugs, which passed the efficacy test in mice, were repeatedly not successful in clinical trials...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731434/passive-assessment-of-routine-driving-with-unobtrusive-sensors-a-new-approach-for-identifying-and-monitoring-functional-level-in-normal-aging-and-mild-cognitive-impairment
#17
Adriana Seelye, Nora Mattek, Nicole Sharma, Phelps Witter, Ariella Brenner, Katherine Wild, Hiroko Dodge, Jeffrey Kaye
BACKGROUND: Driving is a key functional activity for many older adults, and changes in routine driving may be associated with emerging cognitive decline due to early neurodegenerative disease. Current methods for assessing driving such as self-report are inadequate for identifying and monitoring subtle changes in driving patterns that may be the earliest signals of functional change in developing mild cognitive impairment (MCI). OBJECTIVE: This proof of concept study aimed to establish the feasibility of continuous driving monitoring in a sample of cognitively normal and MCI older adults for an average of 206 days using an unobtrusive driving sensor and demonstrate that derived sensor-based driving metrics could effectively discriminate between MCI and cognitively intact groups...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731430/neuroimaging-feature-terminology-a-controlled-terminology-for-the-annotation-of-brain-imaging-features
#18
Anandhi Iyappan, Erfan Younesi, Alberto Redolfi, Henri Vrooman, Shashank Khanna, Giovanni B Frisoni, Martin Hofmann-Apitius
Ontologies and terminologies are used for interoperability of knowledge and data in a standard manner among interdisciplinary research groups. Existing imaging ontologies capture general aspects of the imaging domain as a whole such as methodological concepts or calibrations of imaging instruments. However, none of the existing ontologies covers the diagnostic features measured by imaging technologies in the context of neurodegenerative diseases. Therefore, the Neuro-Imaging Feature Terminology (NIFT) was developed to organize the knowledge domain of measured brain features in association with neurodegenerative diseases by imaging technologies...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731040/er-stress-and-the-unfolded-protein-response-in-neurodegeneration
#19
REVIEW
Claudio Hetz, Smita Saxena
The clinical manifestation of neurodegenerative diseases is initiated by the selective alteration in the functionality of distinct neuronal populations. The pathology of many neurodegenerative diseases includes accumulation of misfolded proteins in the brain. In physiological conditions, the proteostasis network maintains normal protein folding, trafficking and degradation; alterations in this network - particularly disturbances to the function of endoplasmic reticulum (ER) - are thought to contribute to abnormal protein aggregation...
July 21, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28730967/microglia-and-astrocytes-in-alzheimer-s-disease-implications-for-therapy
#20
Marc Fakhoury
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid β peptide and the formation of neurofibrillary tangles (NFTs) in the brain. Over the past few years, mounting evidence has implicated sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD...
July 19, 2017: Current Neuropharmacology
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