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https://www.readbyqxmd.com/read/29142138/chitotriosidase-chit1-is-increased-in-microglia-and-macrophages-in-spinal-cord-of-amyotrophic-lateral-sclerosis-and-cerebrospinal-fluid-levels-correlate-with-disease-severity-and-progression
#1
Petra Steinacker, Federico Verde, Lubin Fang, Emily Feneberg, Patrick Oeckl, Sigrun Roeber, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Hans Foerstl, Armin Giese, Holger Jahn, Jan Kassubek, Johannes Kornhuber, G Bernhard Landwehrmeyer, Martin Lauer, Elmar Hans Pinkhardt, Johannes Prudlo, Angela Rosenbohm, Anja Schneider, Matthias L Schroeter, Hayrettin Tumani, Christine A F von Arnim, Jochen Weishaupt, Patrick Weydt, Albert C Ludolph, Deniz Yilmazer Hanke, Markus Otto
OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con)...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#2
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29115051/to-the-end-of-the-line-axonal-mrna-transport-and-local-translation-in-health-and-neurodegenerative-disease
#3
REVIEW
Christopher J Costa, Dianna E Willis
Axons and growth cones, by their very nature far removed from the cell body, encounter unique environments and require distinct populations of proteins. It seems only natural, then, that they have developed mechanisms to locally synthesize a host of proteins required to perform their specialized functions. Acceptance of this ability has taken decades; however, there is now consensus that axons do indeed have the capacity for local translation, and that this capacity is even retained into adulthood. Accumulating evidence supports the role of locally synthesized proteins in the proper development, maintenance, and function of neurons, and newly emerging studies also suggest that disruption in this process has implications in a number of neurodevelopmental and neurodegenerative diseases...
November 7, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29109789/nucleic-acid-based-theranostics-for-tackling-alzheimer-s-disease
#4
REVIEW
Madhuri Chakravarthy, Suxiang Chen, Peter R Dodd, Rakesh N Veedu
Nucleic acid-based technologies have received significant interest in recent years as novel theranostic strategies for various diseases. The approval by the United States Food and Drug Administration (FDA) of Nusinersen, an antisense oligonucleotide drug, for the treatment of spinal muscular dystrophy highlights the potential of nucleic acids to treat neurological diseases, including Alzheimer's disease (AD). AD is a devastating neurodegenerative disease characterized by progressive impairment of cognitive function and behavior...
2017: Theranostics
https://www.readbyqxmd.com/read/29057990/spinal-cord-injury-and-alzheimer-s-disease-risk-a-population-based-retrospective-cohort-study
#5
Tian-Shin Yeh, Yu-Chun Ho, Cherng-Lan Hsu, Shin-Liang Pan
STUDY DESIGN: Propensity score-matched, retrospective cohort study. OBJECTIVES: To determine the risk of developing Alzheimer's disease (AD) in patients with spinal cord injury (SCI). SETTING: The present study used Taiwan's National Health Insurance Research Database. METHODS: A total of 9257 patients who had ⩾2 ambulatory visits with a diagnosis of SCI in 2001 were included in the SCI group. The non-SCI group consisted of 37,028 propensity score-matched patients without a diagnosis of SCI...
October 23, 2017: Spinal Cord
https://www.readbyqxmd.com/read/29029390/extracellular-truncated-tau-causes-early-presynaptic-dysfunction-associated-with-alzheimer-s-disease-and-other-tauopathies
#6
Fulvio Florenzano, Corsetti Veronica, Gabriele Ciasca, Maria Teresa Ciotti, Anna Pittaluga, Gunedalina Olivero, Marco Feligioni, Filomena Iannuzzi, Valentina Latina, Michele Francesco Maria Sciacca, Alessandro Sinopoli, Danilo Milardi, Giuseppe Pappalardo, De Spirito Marco, Massimiliano Papi, Anna Atlante, Antonella Bobba, Antonella Borreca, Pietro Calissano, Giuseppina Amadoro
The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting potential extracellular role(s) of NH2 -derived fragments of protein on synaptic dysfunction underlying neurodegenerative tauopathies, including Alzheimer's disease (AD). Here we show that sub-toxic doses of extracellular-applied human NH2 tau 26-44 (aka NH 2 htau) -which is the minimal active moiety of neurotoxic 20-22kDa peptide accumulating in vivo at AD synapses and secreted into parenchyma- acutely provokes presynaptic deficit in K(+) -evoked glutamate release on hippocampal synaptosomes along with alteration in local Ca(2+) dynamics...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29024655/lost-in-transportation-nucleocytoplasmic-transport-defects-in-als-and-other-neurodegenerative-diseases
#7
REVIEW
Hong Joo Kim, J Paul Taylor
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by degeneration of upper and lower motor neurons in the brain and spinal cord. The hallmark pathological feature in most cases of ALS is nuclear depletion and cytoplasmic accumulation of the protein TDP-43 in degenerating neurons. Consistent with this pattern of intracellular protein redistribution, impaired nucleocytoplasmic trafficking has emerged as a mechanism contributing to ALS pathology. Dysfunction in nucleocytoplasmic transport is also an emerging theme in physiological aging and other related neurodegenerative diseases, such as Huntington's and Alzheimer's diseases...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/28966628/optogenetics-and-its-application-in-neural-degeneration-and-regeneration
#8
REVIEW
Josue D Ordaz, Wei Wu, Xiao-Ming Xu
Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited...
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28965171/targeting-of-disordered-proteins-by-small-molecules-in-neurodegenerative-diseases
#9
Francesca Longhena, PierFranco Spano, Arianna Bellucci
The formation of protein aggregates and inclusions in the brain and spinal cord is a common neuropathological feature of a number of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and many others. These are commonly referred as neurodegenerative proteinopathies or protein-misfolding diseases. The main characteristic of protein aggregates in these disorders is the fact that they are enriched in amyloid fibrils. Since protein aggregation is considered to play a central role for the onset of neurodegenerative proteinopathies, research is ongoing to develop strategies aimed at preventing or removing protein aggregation in the brain of affected patients...
October 1, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28963550/proteomic-mapping-of-differentially-vulnerable-pre-synaptic-populations-identifies-regulators-of-neuronal-stability-in-vivo
#10
Maica Llavero Hurtado, Heidi R Fuller, Andrew M S Wong, Samantha L Eaton, Thomas H Gillingwater, Giuseppa Pennetta, Jonathan D Cooper, Thomas M Wishart
Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3 (-/-) mouse model of a juvenile form of NCL...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28940129/the-role-of-smurf1-in-neuronal-necroptosis-after-lipopolysaccharide-induced-neuroinflammation
#11
Lifei Shao, Xiaojuan Liu, Shunxing Zhu, Chun Liu, Yilu Gao, Xide Xu
The role of inflammation in neurological disorders such as Alzheimer's disease and Parkinson's disease is gradually recognized and leads to an urgent challenge. Smad ubiquitination regulatory factor 1 (Smurf1), one member of the HECT family, is up-regulated by proinflammatory cytokines and associated with apoptosis in acute spinal cord injury. However, the function of Smurf1 through promoting neuronal necroptosis is still limited in the central nervous system (CNS). Hence, we developed a neuroinflammatory model in adult rats following lipopolysaccharide (LPS) lateral ventral injection to elaborate whether Smurf1 is involved in necroptosis in CNS injury...
September 22, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28912161/disruption-of-bmal1-impairs-blood-brain-barrier-integrity-via-pericyte-dysfunction
#12
Ryota Nakazato, Kenji Kawabe, Daisuke Yamada, Shinsuke Ikeno, Michihiro Mieda, Shigeki Shimba, Eiichi Hinoi, Yukio Yoneda, Takeshi Takarada
Circadian rhythm disturbances are well established in neurological diseases. However, how these disruptions cause homeostatic imbalances remains poorly understood. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) is a major circadian clock transcriptional activator, and Bmal1 deficiency in male Bmal1nestin(-/-) mice induced marked astroglial activation without affecting the number of astrocytes in the brain and spinal cord. Bmal1 deletion caused blood-brain barrier (BBB) hyperpermeability with an age-dependent loss of pericyte coverage of blood vessels in the brain...
October 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28889992/astrocytic-expression-of-the-cxcl12-receptor-cxcr7-ackr3-is-a-hallmark-of-the-diseased-but-not-developing-cns
#13
Malte Puchert, Fabian Pelkner, Gregor Stein, Doychin N Angelov, Johannes Boltze, Daniel-Christoph Wagner, Francesca Odoardi, Alexander Flügel, Wolfgang J Streit, Jürgen Engele
Based on our previous demonstration of CXCR7 as the major mediator of CXCL12 signaling in cultured astrocytes, we have now compared astrocytic expression of the CXCL12 receptors, CXCR7 and CXCR4, during CNS development and disease. In addition, we asked whether disease-associated conditions/factors affect expression of CXCL12 receptors in astrocytes. In the late embryonic rat brain, CXCR7(+)/GFAP(+) cells were restricted to the ventricular/subventricular zone while CXCR4 was widely absent from GFAP-positive cells...
September 8, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28877271/spinal-cord-homogenates-from-sod1-familial-amyotrophic-lateral-sclerosis-induce-sod1-aggregation-in-living-cells
#14
Edward Pokrishevsky, Ran Ha Hong, Ian R Mackenzie, Neil R Cashman
Mutant Cu/Zn superoxide dismutase (SOD1) can confer its misfolding on wild-type SOD1 in living cells; the propagation of misfolding can also be transmitted between cells in vitro. Recent studies identified fluorescently-tagged SOD1G85R as a promiscuous substrate that is highly prone to aggregate by a variety of templates, in vitro and in vivo. Here, we utilized several SOD1-GFP reporter proteins with G37R, G85R, or G93A mutations in SOD1. We observed that human spinal cord homogenates prepared from SOD1 familial ALS (FALS) can induce significantly more intracellular reporter protein aggregation than spinal cord homogenates from sporadic ALS, Alzheimer's disease, multiple system atrophy or healthy control individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28861160/long-nonding-rna-uca1-regulates-neural-stem-cell-differentiation-by-controlling-mir-1-hes1-expression
#15
Jiaolin Zheng, Dan Yi, Yu Liu, Mingqiu Wang, Yulan Zhu, Huaizhang Shi
Neural stem cells are able to self-renew and generate glial and neuronal lineages. Neural stem cell may serve as therapeutic method for neurological disorders including spinal cord injuries, Parkinson's disease, Huntington's disease and Alzheimer's disease. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides with limited protein-coding capacity. Recent studies have demonstreated that lncRNAs play an important role in several cellular processes including cell differentiation, cell development, proliferation, apoptosis, invasion and migration...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28831921/in-silico-studies-in-drug-research-against-neurodegenerative-diseases
#16
Farahnaz Rezaei Makhouri, Jahan B Ghasemi
Neurodegenerative diseases such as Alzheimer's disease (AD), progressive neurodegenerative forms of Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis, spinal cerebellar ataxias, and spinal and bulbar muscular atrophy are described by slow and selective dysfunction and degeneration of neurons and axons in the central nervous system (CNS). Computer-aided or in silico design methods have matured into powerful tools for reducing the number of ligands that should be screened in experimental assays...
August 22, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28818082/comparing-chronic-condition-rates-using-icd-9-and-icd-10-in-va-patients-fy2014-2016
#17
Jean Yoon, Adam Chow
BACKGROUND: Management of patients with chronic conditions relies on accurate measurement. It is unknown how transition to the ICD-10 coding system affected reporting of chronic condition rates over time. We measured chronic condition rates 2 years before and 1 year after the transition to ICD-10 to examine changes in prevalence rates and potential measurement issues in the Veterans Affairs (VA) health care system. METHODS: We developed definitions for 34 chronic conditions using ICD-9 and ICD-10 codes and compared the prevalence rates of these conditions from FY2014 to 2016 in a 20% random sample (1...
August 17, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28782028/computational-integration-of-nanoscale-physical-biomarkers-and-cognitive-assessments-for-alzheimer-s-disease-diagnosis-and-prognosis
#18
Tao Yue, Xinghua Jia, Jennifer Petrosino, Leming Sun, Zhen Fan, Jesse Fine, Rebecca Davis, Scott Galster, Jeff Kuret, Douglas W Scharre, Mingjun Zhang
With the increasing prevalence of Alzheimer's disease (AD), significant efforts have been directed toward developing novel diagnostics and biomarkers that can enhance AD detection and management. AD affects the cognition, behavior, function, and physiology of patients through mechanisms that are still being elucidated. Current AD diagnosis is contingent on evaluating which symptoms and signs a patient does or does not display. Concerns have been raised that AD diagnosis may be affected by how those measurements are analyzed...
July 2017: Science Advances
https://www.readbyqxmd.com/read/28769864/study-on-analysis-of-peripheral-biomarkers-for-alzheimer-s-disease-diagnosis
#19
Palaniswamy Rani, Sreeram Krishnan, Chellappa Rani Cathrine
Many factors are involved in Alzheimer's disease (AD) pathology including tau phosphorylation, amyloid β protein (Aβ) accumulation, lipid dysregulation, oxidative stress, and inflammation. The markers of these pathological processes in cerebral spinal fluid are used currently for AD diagnosis. However, peripheral biomarkers are the need of the hour for large population screening for AD. The main objective of the present study is to evaluate the peripheral levels of redox markers, lipid peroxidation (LPO) indicators, and pathological markers in AD patients...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28761431/synaptosomal-associated-protein-25-may-be-an-intervention-target-for-improving-sensory-and-locomotor-functions-after-spinal-cord-contusion
#20
Zhan-Qiong Zhong, Yang Xiang, Xi Hu, You-Cui Wang, Xi Zeng, Xiao-Meng Wang, Qing-Jie Xia, Ting-Hua Wang, Xiao Zhang
Synaptosomal-associated protein 25 kDa (SNAP-25) is localized on the synapse and participates in exocytosis and neurotransmitter release. Decreased expression of SNAP-25 is associated with Alzheimer's disease and attention deficit/hyperactivity disorder. However, the expression of SNAP-25 in spinal cord contusion injury is still unclear. We hypothesized that SNAP-25 is associated with sensory and locomotor functions after spinal cord injury. We established rat models of spinal cord contusion injury to detect gene changes with a gene array...
June 2017: Neural Regeneration Research
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