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https://www.readbyqxmd.com/read/28639617/gene-therapy-for-spinomuscular-atrophy-a-biomedical-advance-a-missed-opportunity-for-more-equitable-drug-pricing
#1
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
#2
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
#3
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, while 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
#4
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
#5
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)...
June 14, 2017: Neurology
https://www.readbyqxmd.com/read/28611571/exosomes-and-homeostatic-synaptic-plasticity-are-linked-to-each-other-and-to-huntington-s-parkinson-s-and-other-neurodegenerative-diseases-by-database-enabled-analyses-of-comprehensively-curated-datasets
#6
James K T Wang, Peter Langfelder, Steve Horvath, Michael J Palazzolo
Huntington's disease (HD) is a progressive and autosomal dominant neurodegeneration caused by CAG expansion in the huntingtin gene (HTT), but the pathophysiological mechanism of mutant HTT (mHTT) remains unclear. To study HD using systems biological methodologies on all published data, we undertook the first comprehensive curation of two key PubMed HD datasets: perturbation genes that impact mHTT-driven endpoints and therefore are putatively linked causally to pathogenic mechanisms, and the protein interactome of HTT that reflects its biology...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28603767/lumbar-puncture-in-patients-with-neurologic-conditions
#7
Rosha Babapour Mofrad, Femke H Bouwman, Rosalinde E R Slot, Tessa Timmers, Wiesje M van der Flier, Philip Scheltens, Charlotte E Teunissen
A lumbar puncture is performed to obtain cerebral spinal fluid. It is implemented in the clinic on a routine basis to aid the diagnosis of neurologic diseases, such as dementia. This video will show the lumbar puncture procedure as routinely performed in the VUmc Alzheimer Center.
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28588547/improving-dual-task-walking-paradigms-to-detect-prodromal-parkinson-s-and-alzheimer-s-diseases
#8
Maroua Belghali, Nathalie Chastan, Damien Davenne, Leslie M Decker
Gait control is a complex movement, relying on spinal, subcortical, and cortical structures. The presence of deficits in one or more of these structures will result in changes in gait automaticity and control, as is the case in several neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). By reviewing recent findings in this field of research, current studies have shown that gait performance assessment under dual-task conditions could contribute to predict both of these diseases...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28582450/spontaneous-low-frequency-bold-signal-variations-from-resting-state-fmri-are-decreased-in-alzheimer-disease
#9
Samaneh Kazemifar, Kathryn Y Manning, Nagalingam Rajakumar, Francisco A Gómez, Andrea Soddu, Michael J Borrie, Ravi S Menon, Robert Bartha
Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative...
2017: PloS One
https://www.readbyqxmd.com/read/28577973/membrane-lipid-therapy-a-historical-perspective-of-membrane-targeted-therapies-from-lipid-bilayer-structure-to-the-pathophysiological-regulation-of-cells
#10
EDITORIAL
Pablo V Escribá
Our current understanding of membrane lipid composition, structure and functions has led to the investigation of their role in cell signaling, both in healthy and pathological cells. As a consequence, therapies based on the regulation of membrane lipid composition and structure have been recently developed. This novel field, known as Membrane Lipid Therapy, is growing and evolving rapidly, providing treatments that are now in use or that are being studied for their application to oncological disorders, Alzheimer's disease, spinal cord injury, stroke, diabetes, obesity, and neuropathic pain...
June 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28539884/the-analysis-of-two-bdnf-polymorphisms-g196a-c270t-in-chinese-sporadic-amyotrophic-lateral-sclerosis
#11
Lianping Xu, Danyang Tian, Jiao Li, Lu Chen, Lu Tang, Dongsheng Fan
Amyotrophic lateral sclerosis (ALS) is an ethnically heterogeneous motor neuron disease that results from the selective death of motor neurons in the brain and spinal cord. Brain-derived neurotrophic factor (BDNF) is widely distributed across the central and peripheral nervous systems and plays neurotrophic and other physiological roles in various brain regions. Alterations of neurotrophin availability have been proposed as a pathogenic mechanism underlying ALS neurodegeneration. Several genetic studies have shown a significant association between schizophrenia, Alzheimer's disease, and Parkinson's disease and certain BDNF polymorphisms, specifically G196A (rs6265) and C270T (rs56164415)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28526745/identification-and-characterisation-of-nanobodies-targeting-the-epha4-receptor
#12
Lies Schoonaert, Laura Rué, Bart Roucourt, Mieke Timmers, Susan Little, Lucía Chávez Gutiérrez, Maarten Dewilde, Peter Joyce, Adam Curnock, Peter Weber, Jurgen Haustraete, Gholamreza Hassanzadeh-Ghassabeh, Bart De Strooper, Ludo Van Den Bosch, Philip Van Damme, Robin Lemmens, Wim Robberecht
The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28508364/a-novel-2-de-based-proteomic-analysis-to-identify-multiple-substrates-for-specific-protease-in-neuronal-cells
#13
Chiho Kim, Young J Oh
Proteolysis is a process where proteins are broken down into smaller polypeptides or amino acids, comprising one of the important posttranslational modifications of proteins. Since this process is exquisitely achieved by specialized enzymes called proteases under physiological conditions, abnormal protease activity and dysregulation of their substrate proteins are closely associated with a progression of several neurodegenerative diseases including Alzheimer disease, Parkinson disease, stroke, and spinal cord injury...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28505972/alzheimer-s-disease-associated-cerebrospinal-fluid-csf-biomarkers-do-not-correlate-with-csf-volumes-or-csf-production-rate
#14
Mikael Edsbagge, Ulf Andreasson, Khalid Ambarki, Carsten Wikkelsø, Anders Eklund, Kaj Blennow, Henrik Zetterberg, Mats Tullberg
BACKGROUND: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28498801/extracellular-truncated-tau-causes-early-presynaptic-dysfunction-associated-with-alzheimer-s-disease-and-other-tauopathies
#15
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, Marco De Spirito, 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 NH2tau 26-44 (aka NH2htau) -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 Ca2+ dynamics...
April 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28476630/membrane-lipid-therapy-a-historical-perspective-of-membrane-targeted-therapies-from-lipid-bilayer-structure-to-the-pathophysiological-regulation-of-cells
#16
REVIEW
Pablo V Escribá
Our current understanding of membrane lipid composition, structure and functions has led to the investigation of their role in cell signaling, both in healthy and pathological cells. As a consequence, therapies based on the regulation of membrane lipid composition and structure have been recently developed. This novel field, known as membrane lipid therapy, is growing and evolving rapidly, providing treatments that are now in use or that are being studied for their application to oncological disorders, Alzheimer's disease, spinal cord injury, stroke, diabetes, obesity, and neuropathic pain...
May 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#17
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28444635/the-leukocentric-theory-of-neurological-disorder-a-manifesto
#18
Robert Fern
Approximately half of the human brain is composed of white matter (WM), a specialized tissue housing the axonal projection of neurons and their necessary supporting glial cells. Axons course long distances from their parent soma, have a delicate structure, large surface area and in many cases are dependent upon a uniquely close morphological arrangement with myelinating oligodendrocyte partners; all factors that may predispose them to injury and disease. WM damage is central to a range of well-characterized disorders including multiple sclerosis and spinal cord injury and is also makes a significant contribution to disorders often considered to be largely focused in gray matter; for example, in stroke where ~49% of injury by volume is located in WM...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28442357/dl-3-n-butylphthalide-promotes-neuroplasticity-and-motor-recovery-in-stroke-rats
#19
Yefei Sun, Xi Cheng, Huibin Wang, Xiaopeng Mu, Yifan Liang, YuJia Luo, Huiling Qu, Chuansheng Zhao
BACKGROUNDS AND AIMS: Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia. METHODS: Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70mg/kg dl-NBP by oral gavage for two weeks...
June 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#20
REVIEW
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
June 2017: Expert Opinion on Therapeutic Targets
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