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Neurodegenerative diseases

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https://www.readbyqxmd.com/read/29332044/does-the-genetic-feature-of-the-chinese-tree-shrew-tupaia-belangeri-chinensis-support-its-potential-as-a-viable-model-for-alzheimer-s-disease-research
#1
Yu Fan, Rongcan Luo, Ling-Yan Su, Qun Xiang, Dandan Yu, Ling Xu, Jia-Qi Chen, Rui Bi, Dong-Dong Wu, Ping Zheng, Yong-Gang Yao
Alzheimer's disease (AD) is a neurodegenerative disease with increasing incidence across the world and no cure at the present time. An ideal animal model would facilitate the understanding of the pathogenesis of AD and discovery of potential therapeutic targets. The Chinese tree shrew (Tupaia belangeri chinensis) has a closer genetic affinity to primates relative to rodents, and can attain ages of 8 years or older, which represents another advantage for the study of neurodegenerative diseases such as AD compared to primates...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332010/oligogenic-genetic-variation-of-neurodegenerative-disease-genes-in-980-postmortem-human-brains
#2
Michael J Keogh, Wei Wei, Juvid Aryaman, Ian Wilson, Kevin Talbot, Martin R Turner, Chris-Anne McKenzie, Claire Troakes, Johannes Attems, Colin Smith, Safa Al Sarraj, Chris M Morris, Olaf Ansorge, Stuart Pickering-Brown, Nick Jones, James W Ironside, Patrick F Chinnery
BACKGROUND: Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series. METHODS: We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls...
January 13, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29331938/generation-of-a-human-induced-pluripotent-stem-cell-line-csc-40-from-a-parkinson-s-disease-patient-with-a-pink1-p-q456x-mutation
#3
Kaspar Russ, Ana Marote, Ekaterina Savchenko, Anna Collin, Stefano Goldwurm, Yuriy Pomeshchik, Laurent Roybon
Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology. Here we show the generation of an induced pluripotent stem cell (iPSC) line, named CSC-40, from dermal fibroblasts obtained from a 59-year-old male patient with a homozygous p.Q456X mutation in the PTEN-induced putative kinase 1 (PINK/PARK6) gene and a confirmed diagnosis of PD, which could be used to model familial PD. A non-integrating Sendai virus-based delivery of the reprogramming factors OCT3/4, SOX2, c-MYC and KLF4 was employed...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29331872/effect-of-physical-activity-on-cognitive-flexibility-depression-and-rbd-in-healthy-elderly
#4
Stefanie Lerche, Alexandra Gutfreund, Kathrin Brockmann, Markus A Hobert, Isabel Wurster, Ulrike Sünkel, Gerhard W Eschweiler, Florian G Metzger, Walter Maetzler, Daniela Berg
OBJECTIVE: The prevalence of Alzheimer's disease and Parkinson's disease increases with the raising number of elderly, which will be a challenging situation for the healthcare systems and society in the future. There is evidence that there are modifiable risk-factors e.g. physical activity for these diseases. Here, we study the interaction between sports inactivity with prodromal markers for neurodegeneration. PATIENTS AND METHODS: We investigated 667 neurologically healthy individuals cross-sectional and a subgroup longitudinal over six years...
January 9, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29331848/repetitive-transcranial-magnetic-stimulation-for-apathy-in-mild-cognitive-impairment-a-double-blind-randomized-sham-controlled-cross-over-pilot-study
#5
Prasad R Padala, Kalpana P Padala, Shelly Y Lensing, Andrea N Jackson, Cassandra R Hunter, Christopher M Parkes, Richard A Dennis, Melinda M Bopp, Ricardo Caceda, Mark S Mennemeier, Paula K Roberson, Dennis H Sullivan
Apathy is a common and disabling behavioral concomitant of many neurodegenerative conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked with heightened rates of conversion to Alzheimer's disease. Improving apathy may slow the neurodegenerative process. The objective was to establish the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross-over study was conducted in nine subjects (66 ± 9 years) with apathy and MCI...
January 5, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29331395/tyrosine-hydroxylase-as-a-sentinel-for-central-and-peripheral-tissue-responses-in-parkinson-s-progression-evidence-from-clinical-studies-and-neurotoxin-models
#6
REVIEW
M E Johnson, M F Salvatore, S A Maiolo, L Bobrovskaya
Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While the typical motor symptoms of PD are well known, the lesser known non-motor symptoms can also greatly impact the patient's quality of life. These symptoms often appear before motor impairment, therefore identifying biomarkers that may predict PD risk or pathology has been a major and challenging endeavour. Given that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH) occurs in PD, the expression and accompanying post-translational changes in TH during PD progression could yield insight into the disruption of cellular signalling occurring in the CNS, and also in peripheral tissues wherein catecholamine function plays a role...
January 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29331073/cerebrospinal-fluid-macrophage-biomarkers-in-amyotrophic-lateral-sclerosis
#7
A G Thompson, E Gray, M-L Thézénas, P D Charles, S Evetts, M T Hu, K Talbot, R Fischer, B M Kessler, M R Turner
Objective The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid samples. Methods Liquid chromatography-tandem mass spectrometry with label-free quantification was used to identify cerebrospinal fluid proteins using samples from a well-characterised longitudinal cohort comprising patients with ALS (n=43), the upper motor neuron variant primary lateral sclerosis (PLS, n=6), cross-sectional healthy (n=20) and disease controls (Parkinsons's n=20, ALS mimic disorders n=12)...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29330409/induction-of-ferroptosis-and-mitochondrial-dysfunction-by-oxidative-stress-in-pc12-cells
#8
Chuanhong Wu, Wenwen Zhao, Jie Yu, Shaojing Li, Ligen Lin, Xiuping Chen
Neurodegenerative diseases (NDD) are typically associated with neuron loss in nervous system areas. Interventions with related death mechanisms may ameliorate NDD progression. Oxidative stress plays an important role in NDD cell death routines. However, tert-butylhydroperoxide (t-BHP), a widely used oxidative stress stimulus, induces neural cell death through a mechanism that remains elusive. In our study, the ferroptosis marker events occurred after co-treatment with 100 μM t-BHP for 1 h, all of which were reversed in the presence of the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine, implying the occurrence of ferroptosis...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330304/efficient-prion-disease-transmission-through-common-environmental-materials
#9
Sandra Pritzkow, Rodrigo Morales, Adam Lyon, Luis Concha-Marambio, Akihiko Urayama, Claudio Soto
Prion diseases are a group of fatal neurodegenerative diseases associated with a protein-based infectious agent, termed prion. Compelling evidence suggests that natural transmission of prion diseases is mediated by environmental contamination with infectious prions. We hypothesized that several natural and man-made materials, commonly found in the environments of wild and captive animals, can bind prions and may act as vectors for disease transmission. To test our hypothesis, we exposed surfaces composed of various common environmental materials (i...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29330223/the-anti-oxidant-xanthorrhizol-prevents-amyloid-%C3%AE-induced-oxidative-modification-and-inactivation-of-neprilysin
#10
Chol Seung Lim, Jung-Soo Han
Activity of neprilysin (NEP), the major protease which cleaves β-amyloid (Aβ), is reportedly reduced in the brains of patients with Alzheimer's disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxy nonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess anti-oxidant and anti-inflammatory properties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced oxidative modification of NEP protein...
January 12, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29330136/white-matter-volume-loss-in-amyotrophic-lateral-sclerosis-a-meta-analysis-of-voxel-based-morphometry-studies
#11
REVIEW
Guangxiang Chen, Baiwan Zhou, Hongyan Zhu, Weihong Kuang, Feng Bi, Hua Ai, Zhongwei Gu, Xiaoqi Huang, Su Lui, Qiyong Gong
Structural neuroimaging studies of white matter (WM) volume in amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded inconsistent findings. This study aimed to perform a quantitative voxel-based meta-analysis using effect-size signed differential mapping (ES-SDM) to establish a statistical consensus between published studies for WM volume alterations in ALS. The pooled meta-analysis revealed significant WM volume losses in the bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left middle cerebellar peduncle and right cerebellum in patients with ALS, involving the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract...
January 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29330065/stargazin-differentially-modulates-ampakine-gating-kinetics-and-pharmacology
#12
Daniel P Radin, Yong-Xin Li, Gary Rogers, Richard Purcell, Arnold Lippa
It was previously reported that Stargazin (STG) enhances the surface expression of AMPA receptors, controls receptor gating and slows channel desensitization as an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor positive allosteric modulators that modify rates of transmitter binding, channel activity and desensitization parameters. As such, they have shown efficacy in animal models of neurodegenerative diseases, where excitatory synaptic transmission is compromised. Given the functional similarities between STG and ampakines, the current study sought to probe interactions between STG and ampakine gating properties...
January 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29330040/yod1-attenuates-neurogenic-proteotoxicity-through-its-deubiquitinating-activity
#13
Kunikazu Tanji, Fumiaki Mori, Yasuo Miki, Jun Utsumi, Hidenao Sasaki, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
Ubiquitination, a fundamental post-translational modification of intracellular proteins, is enzymatically reversed by deubiquitinase enzymes (deubiquitinases). >90 deubiquitinases have been identified. One of these enzymes, YOD1, possesses deubiquitinase activity and is similar to ovarian tumor domain-containing protein 1, which is associated with regulation of the endoplasmic reticulum (ER)-associated degradation pathway. Indeed, YOD1 is reported to be involved in the ER stress response induced by mislocalization of unfolded proteins in mammalian cells...
January 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29330017/a-wrapped-multi-label-classifier-for-the-automatic-diagnosis-and-prognosis-of-alzheimer-s-disease
#14
C Salvatore, I Castiglioni
BACKGROUND: AD is the most frequent neurodegenerative disease, severely impacting our society. Early diagnosis and prognosis are challenging tasks in the management of AD patients. NEW METHOD: We implemented a machine-learning classifier for the automatic early diagnosis and prognosis of AD by means of features extracted, selected and optimized from structural MRI brain images. The classifier was designed to perform multi-label automatic classification into the following four classes: HC, ncMCI, cMCI, and AD...
January 9, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29329976/therapeutic-potential-of-spinal-glp-1-receptor-signaling
#15
REVIEW
Dongao Zhang, Gang Lv
GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease...
January 9, 2018: Peptides
https://www.readbyqxmd.com/read/29329719/regulatory-potential-of-the-rna-processing-machinery-implications-for-human-disease
#16
REVIEW
Kirstyn T Carey, Vihandha O Wickramasinghe
Splicing and nuclear export of mRNA are critical steps in the gene expression pathway. While RNA processing factors can perform general, essential functions for intron removal and bulk export of mRNA, emerging evidence highlights that the core RNA splicing and export machineries also display regulatory potential. Here, we discuss recent insights into how this regulatory potential can selectively alter gene expression and regulate important biological processes. We also highlight the participation of RNA processing pathways in the cellular response to DNA damage at multiple levels...
January 9, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29329610/bacopa-monnieri-extracts-prevent-hydrogen-peroxide-induced-oxidative-damage-in-a-cellular-model-of-neuroblastoma-imr32-cells
#17
Gaurav Bhatia, Vikram Dhuna, Kshitija Dhuna, Manpreet Kaur, Jatinder Singh
Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide (H2O2), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against H2O2 induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29329581/microrna-124-regulates-the-expression-of-mekk3-in-the-inflammatory-pathogenesis-of-parkinson-s-disease
#18
Longping Yao, Yongyi Ye, Hengxu Mao, Fengfei Lu, Xiaozheng He, Guohui Lu, Shizhong Zhang
BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29329108/cracking-novel-shared-targets-between-epilepsy-and-alzheimer-s-disease-need-of-the-hour
#19
Nitika Garg, Rupa Joshi, Bikash Medhi
Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that seizures are linked with cognitive impairment, and there are various shared etiologies between epilepsy and AD. The connection between hyperexcitability of neurons and cognitive dysfunction in the progression of AD or epileptogenesis plays a vital role for improving selection of treatment for both diseases. Traditionally, seizures occur less frequently and in later stages of age in patients with AD which in turn implies that neurodegeneration causes seizures...
January 12, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29328983/social-and-cognitive-control-skills-in-long-life-occupation-activities-modulate-the-brain-reserve-in-the-behavioural-variant-of-frontotemporal-dementia
#20
Alessandra Dodich, Giulia Carli, Chiara Cerami, Sandro Iannaccone, Giuseppe Magnani, Daniela Perani
BACKGROUND: Cognitive reserve may delay disease onset and mitigate symptoms presentation in neurodegenerative dementias. Although high occupation levels can be associated with higher cognitive reserve in the behavioural variant of frontotemporal dementia (bvFTD), it was never addressed how specific occupation profiles involving social interaction, executive and attention abilities can modulate neural reserve in bvFTD. MATERIALS AND METHODS: We retrospectively included thirty-seven bvFTD patients with clinical-neuropsychological and FDG-PET brain metabolic data...
December 19, 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
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