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https://www.readbyqxmd.com/read/28738061/magnetic-resonance-imaging-and-tensor-based-morphometry-in-the-mptp-non-human-primate-model-of-parkinson-s-disease
#1
Michel Modo, William R Crum, Madeline Gerwig, Anthony C Vernon, Priya Patel, Michael J Jackson, Sarah Rose, Peter Jenner, Mahmoud M Iravani
Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD...
2017: PloS One
https://www.readbyqxmd.com/read/28737894/dual-role-of-gold-nanorods-inhibition-dissolution-of-a%C3%AE-fibrils-induced-by-near-ir-laser
#2
Swathi Sudhakar, Poornima Budime Santhosh, Ethayaraja Mani
Extracellular plaques of amyloid beta (Aβ) fibrils and neurofibrillary tangles are known to be associated with neurological diseases such as Alzheimer's. Studies have shown that spherical nanoparticles inhibit the formation of Aβ fibrils by intercepting the nucleation and growth pathways of fibrillation. In this report, gold nanorods (AuNR) are used to inhibit the formation of Aβ fibrils and the shape-dependent plasmonic properties of AuNR are exploited to faciliate faster dissolution of mature Aβ fibrils...
July 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28737745/electromagnetized-gold-nanoparticles-mediate-direct-lineage-reprogramming-into-induced-dopamine-neurons-in-vivo-for-parkinson-s-disease-therapy
#3
Junsang Yoo, Euiyeon Lee, Hee Young Kim, Dong-Ho Youn, Junghyun Jung, Hongwon Kim, Yujung Chang, Wonwoong Lee, Jaein Shin, Soonbong Baek, Wonhee Jang, Won Jun, Soochan Kim, Jongki Hong, Hi-Joon Park, Christopher J Lengner, Sang Hyun Moh, Youngeun Kwon, Jongpil Kim
Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes...
July 17, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28737731/study-on-chemical-profile-and-neuroprotective-activity-of-myrica-rubra-leaf-extract
#4
Pinghong Chen, Xianzong Lin, Ching-Hsu Yang, Xu Tang, Yu-Wei Chang, Weibing Zheng, Lianzhong Luo, Changan Xu, Yung-Husan Chen
The chemical profile of Myrica rubra (a native species in China) leaf extract was investigated by UPLC-PDA-HRMS, and the neuroprotective activity of two characteristic constituents, myricanol and myricetrin, was evaluated with N2a cells using H₂O₂-inducedoxidative challenge through a series of methods, e.g., MTT assay, ROS assay and [Ca(2+)]i assay. Among the 188 constituents detected in the extract of Myrica rubra leaf, 116 were identified definitely or tentatively by the comprehensive utilization of precise molecular weight and abundant multistage fragmentation information obtained by quadrupole orbitrap mass spectrometry...
July 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28737703/autophagy-and-human-neurodegenerative-diseases-a-fly-s-perspective
#5
REVIEW
Myungjin Kim, Allison Ho, Jun Hee Lee
Neurodegenerative diseases in humans are frequently associated with prominent accumulation of toxic protein inclusions and defective organelles. Autophagy is a process of bulk lysosomal degradation that eliminates these harmful substances and maintains the subcellular environmental quality. In support of autophagy's importance in neuronal homeostasis, several genetic mutations that interfere with autophagic processes were found to be associated with familial neurodegenerative disorders. In addition, genetic mutations in autophagy-regulating genes provoked neurodegenerative phenotypes in animal models...
July 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28737695/predictive-structure-and-topology-of-peroxisomal-atp-binding-cassette-abc-transporters
#6
Pierre Andreoletti, Quentin Raas, Catherine Gondcaille, Mustapha Cherkaoui-Malki, Doriane Trompier, Stéphane Savary
The peroxisomal ATP-binding Cassette (ABC) transporters, which are called ABCD1, ABCD2 and ABCD3, are transmembrane proteins involved in the transport of various lipids that allow their degradation inside the organelle. Defective ABCD1 leads to the accumulation of very long-chain fatty acids and is associated with a complex and severe neurodegenerative disorder called X-linked adrenoleukodystrophy (X-ALD). Although the nucleotide-binding domain is highly conserved and characterized within the ABC transporters family, solid data are missing for the transmembrane domain (TMD) of ABCD proteins...
July 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28737687/new-cinchona-oximes-evaluated-as-reactivators-of-acetylcholinesterase-and-butyrylcholinesterase-inhibited-by-organophosphorus-compounds
#7
Maja Katalinić, Antonio Zandona, Alma Ramić, Tamara Zorbaz, Ines Primožič, Zrinka Kovarik
For the last six decades, researchers have been focused on finding efficient reactivators of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study, we have focused our research on a new oxime scaffold based on the Cinchona structure since it was proven to fit the cholinesterases active site and reversibly inhibit their activity. Three Cinchona oximes (C1, C2, and C3), derivatives of the 9-oxocinchonidine, were synthesized and investigated in reactivation of various OP-inhibited AChE and BChE...
July 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28736521/group-level-progressive-alterations-in-brain-connectivity-patterns-revealed-by-diffusion-tensor-brain-networks-across-severity-stages-in-alzheimer-s-disease
#8
Javier Rasero, Carmen Alonso-Montes, Ibai Diez, Laiene Olabarrieta-Landa, Lakhdar Remaki, Iñaki Escudero, Beatriz Mateos, Paolo Bonifazi, Manuel Fernandez, Juan Carlos Arango-Lasprilla, Sebastiano Stramaglia, Jesus M Cortes
Alzheimer's disease (AD) is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer's Disease Neuroimaging Initiative (ADNI), four different groups were defined (all of them matched by age, sex and education level): G1 (N1 = 36, healthy control subjects, Control), G2 (N2 = 36, early mild cognitive impairment, EMCI), G3 (N3 = 36, late mild cognitive impairment, LMCI) and G4 (N4 = 36, AD)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28736435/extracellular-vesicles-in-renal-disease
#9
REVIEW
Diana Karpman, Anne-Lie Ståhl, Ida Arvidsson
Extracellular vesicles, such as exosomes and microvesicles, are host cell-derived packages of information that allow cell-cell communication and enable cells to rid themselves of unwanted substances. The release and uptake of extracellular vesicles has important physiological functions and may also contribute to the development and propagation of inflammatory, vascular, malignant, infectious and neurodegenerative diseases. This Review describes the different types of extracellular vesicles, how they are detected and the mechanisms by which they communicate with cells and transfer information...
July 24, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28736294/enhanced-neuroprotection-of-anthocyanin-loaded-peg-gold-nanoparticles-against-a%C3%AE-1-42-induced-neuroinflammation-and-neurodegeneration-via-the-nf-kb-jnk-gsk3%C3%AE-signaling-pathway
#10
Min Ju Kim, Shafiq Ur Rehman, Faiz Ul Amin, Myeong Ok Kim
Amyloid-beta (Aβ1-42) plaques and neurofibrillary tangles (NFTs) are the main hallmarks considered to be associated with neuroinflammation in Alzheimer's disease (AD). Recently, nanoparticle-based targeted drug delivery approaches have been found to be a useful tool in the neurotherapeutics field. Therefore, we examined and compared the neuroprotective effect of anthocyanins alone and anthocyanin-loaded poly (ethylene glycol)-gold nanoparticles (PEG-AuNPs) in Aβ1-42-injected mouse and in vitro models of AD...
July 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28736195/allelic-difference-in-mhc2ta-confers-altered-microglial-activation-and-susceptibility-to-%C3%AE-synuclein-induced-dopaminergic-neurodegeneration
#11
Itzia Jimenez-Ferrer, Michael Jewett, Ashmita Tontanahal, Marina Romero-Ramos, Maria Swanberg
Parkinson Disease (PD) is a complex and heterogeneous neurodegenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta and pathological intracellular accumulation of alpha-synuclein (α-syn). In the vast majority of PD patients, the disease has a complex etiology, defined by multiple genetic and environmental risk factors. Common genetic variants in the human leukocyte-antigen (HLA) region have been associated to PD risk and the carriage of these can double the risk to develop PD...
July 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28735170/effects-of-different-solvents-on-the-conformations-of-apoptotic-cytochrome-c-structural-insights-from-molecular-dynamics-simulation
#12
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
#13
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
#14
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
#15
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
#16
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/28733928/structural-neurodegeneration-correlates-with-early-diabetic-retinopathy
#17
Ulrik Frydkjaer-Olsen, Rasmus Soegaard Hansen, Tunde Peto, Jakob Grauslund
PURPOSE: To examine differences in structural and functional neurodegenerative measurements between patients with no and early diabetic retinopathy (DR). METHODS: In this cross-sectional study, we examined 103 patients with type 2 diabetes mellitus. In 7-field fundus photographs acquired with Topcon TRC-NW6S, a single, certified grader determined the presence of DR according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral domain optical coherence tomography (OCT) and by a RETI-scan multifocal electroretinography (mf-ERG) system in rings 1-6...
July 21, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#18
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/28733623/crystal-structure-of-a-low-molecular-weight-activator-blm-pep-with-yeast-20s-proteasome-insights-into-the-enzyme-activation-mechanism
#19
Julia Witkowska, Małgorzata Giżyńska, Przemysław Grudnik, Przemysław Golik, Przemysław Karpowicz, Artur Giełdoń, Grzegorz Dubin, Elżbieta Jankowska
Proteasomes are responsible for protein turnover in eukaryotic cells, degrading short-lived species but also removing improperly folded or oxidatively damaged ones. Dysfunction of a proteasome results in gradual accumulation of misfolded/damaged proteins, leading to their aggregation. It has been postulated that proteasome activators may facilitate removal of such aggregation-prone proteins and thus prevent development of neurodegenerative disorders. However, the discovery of pharmacologically relevant compounds is hindered by insufficient structural understanding of the activation process...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733489/interaction-of-misfolded-proteins-and-mitochondria-in-neurodegenerative-disorders
#20
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
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