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https://www.readbyqxmd.com/read/28912161/disruption-of-bmal1-impairs-blood-brain-barrier-integrity-via-pericyte-dysfunction
#1
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...
September 14, 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
#2
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 7, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28754163/choroid-plexus-cerebrospinal-fluid-route-for-monocyte-derived-macrophages-after-stroke
#10
Ruimin Ge, Daniel Tornero, Masao Hirota, Emanuela Monni, Cecilia Laterza, Olle Lindvall, Zaal Kokaia
BACKGROUND: Choroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer's disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after ischemic stroke is unknown. METHODS: Adult male C57BL/6 mice were subjected to focal cortical ischemia by permanent occlusion of the distal branch of the right middle cerebral artery...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28737113/micrornas-roles-in-regulating-neuroinflammation
#11
Andrew D Gaudet, Laura K Fonken, Linda R Watkins, Randy J Nelson, Phillip G Popovich
MicroRNAs (miRNAs) are small noncoding RNAs that broadly affect cellular and physiological function in all multicellular organisms. Here, the role of miRNAs in neuroinflammation is considered. miRNAs are 21- to 23-oligonucleotide RNAs that regulate translation of specific RNAs by binding to complementary regulatory RNA sequences, thereby causing mRNA degradation or sequestration. More than 5000 miRNAs likely exist in humans, and each miRNA binds an average of 200 RNAs. Specific immunomodulatory miRNAs can regulate a set of RNAs in a coordinated manner, suggesting that effective miRNA-based therapeutic manipulations for neuroinflammatory conditions may be revealed...
July 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28726050/a-single-center-study-a%C3%AE-42-p-tau181-csf-ratio-to-discriminate-ad-from-ftd-in-clinical-setting
#12
Andrea Vergallo, Cecilia Carlesi, Cristina Pagni, Filippo Sean Giorgi, Filippo Baldacci, Lucia Petrozzi, Roberto Ceravolo, Gloria Tognoni, Gabriele Siciliano, Ubaldo Bonuccelli
Abnormal levels of beta amyloid (Aβ42) and tau protein concentrations in the cerebral spinal fluid (CSF) have been largely described in Alzheimer's disease (AD). Thus, CSF analysis of these biomarkers has been incorporated in recent AD diagnostic criteria, and it is increasingly performed for neurodegenerative dementia diagnostic workout in clinical setting. Nevertheless, the precise biomarkers CSF features in neurodegenerative dementia, either AD or Frontotemporal dementia (FTD), are still not fully clear today...
July 19, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28685694/multi-targeting-strategies-for-alzheimer-s-disease-therapeutics-pros-and-cons
#13
Sucharita Das, Soumalee Basu
Alzheimer's disease (AD) is a single major cause of dementia in middle to old age individuals involving several different etiopathological mechanisms that are yet to be properly characterized. Major invariant and characteristic features consist of the progressive cerebral deposition of the amyloid β-protein (Aβ) and the neurofibrillary degeneration through neurofibrillary tangles (NFT) formed by hyperphosphorylation of the tau proteins in the regions of the brain that deal with memory and cognition. There are at least five subgroups of AD that can be identified by determining cerebro-spinal fluid (CSF) levels of Aβ1-42, tau and ubiquitin...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28679106/macrophage-migration-inhibitory-factor-a-multifaceted-cytokine-implicated-in-multiple-neurological-diseases
#14
REVIEW
Marcel F Leyton-Jaimes, Joy Kahn, Adrian Israelson
Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated...
July 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28666746/micrornas-as-important-regulators-of-exercise-adaptation
#15
REVIEW
Gustavo J J Silva, Anja Bye, Hamid El Azzouzi, Ulrik Wisløff
A significant body of evidence supports the protective role of exercise training (ET) in cardiovascular diseases, skeletal muscle dystrophies, several types of cancer, Alzheimer disease or even in the recovery of spinal cord injury. In spite of this, the molecular mechanisms underlying the beneficial effects of exercise training are not well understood and remain elusive. Several mechanisms have been proposed in the past, but more recently microRNAs (miRNAs), small non-coding RNA molecules involved in a variety of basic biological processes that negatively modulate gene expression, recognized as important regulatory molecules...
June 2017: Progress in Cardiovascular Diseases
https://www.readbyqxmd.com/read/28639617/gene-therapy-for-spinomuscular-atrophy-a-biomedical-advance-a-missed-opportunity-for-more-equitable-drug-pricing
#16
T Friedmann
An experimental approach for gene therapy of spinomuscular atrophy has been reported to prevent development of the neuromuscular features of this lethal and previously untreatable disorder. The approach involves treatment of patients suffering from SMN1-associated infantile form of the disease with a splice-switching antisense oligonucleotide (ASO) that corrects aberrant splicing of the nearly identical SMN2 gene to allow the generation of functional SMN protein, thereby mitigating the development of the disease...
June 22, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28636676/mitochondrion-to-endoplasmic-reticulum-apposition-length-in-zebrafish-embryo-spinal-progenitors-is-unchanged-in-response-to-perturbations-associated-with-alzheimer-s-disease
#17
Morgan Newman, Lena Halter, Anne Lim, Michael Lardelli
Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD). The length of mitochondrion-endoplasmic reticulum (M-ER) appositions is increased in Psen1-/-/Psen2-/- double knockout murine embryonic fibroblasts and in fibroblasts from AD-affected individuals. Development of an easily accessible, genetically manipulable, in vivo system for studying M-ER appositions would be valuable so we attempted to manipulate M-ER apposition length in zebrafish (Danio rerio) embryos...
2017: PloS One
https://www.readbyqxmd.com/read/28630007/rna-localization-making-its-way-to-the-center-stage
#18
REVIEW
Ashley Chin, Eric Lécuyer
Cells are highly organized entities that rely on intricate addressing mechanisms to sort their constituent molecules to precise subcellular locations. These processes are crucial for cells to maintain their proper organization and carry out specialized functions in the body, consequently genetic perturbations that clog up these addressing systems can contribute to disease aetiology. The trafficking of RNA molecules represents an important layer in the control of cellular organization, a process that is both highly prevalent and for which features of the regulatory machineries have been deeply conserved evolutionarily...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28622692/motor-deficits-are-independent-of-axonopathy-in-an-alzheimer-s-disease-mouse-model-of-tgcrnd8-mice
#19
Qiuju Yuan, Jian Yang, Wutian Wu, Zhi-Xiu Lin
There have been an increasing number of reports of non-cognitive symptoms in Alzheimer's disease (AD). Some symptoms are associated with the loss of motor functions, e.g. gait disturbances, disturbed activity level and balance. Consistent with clinical findings, several AD mouse models harboring amyloid pathology develop motor impairment. Although the factors that contribute to the motor deficits have not yet been determined, it has been suggested that axonopathy is one of the key factors that may contribute to this particular feature of the disease...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615436/hospital-safety-among-neurologic-patients-a-population-based-cohort-study-of-adverse-events
#20
MULTICENTER STUDY
Khara M Sauro, Hude Quan, Khokan C Sikdar, Peter Faris, Nathalie Jette
OBJECTIVE: To examine the frequency and type of adverse events (AEs) experienced by neurologic patients in hospital. METHODS: This population-based, retrospective cohort study used hospital discharge abstract data for children and adults admitted to hospital from 2009 to 2015 with 1 of 9 neurologic conditions (Alzheimer disease and related dementia, brain tumor, epilepsy, motor neuron disease, multiple sclerosis, parkinsonism/Parkinson disease, spinal cord injury, traumatic brain injury, and stroke)...
July 18, 2017: Neurology
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