25,067 results match your criteria Amyotrophic Lateral Sclerosis


Inhibition of MEK5 suppresses TDP-43 toxicity via the mTOR-independent activation of the autophagy-lysosome pathway.

Biochem Biophys Res Commun 2019 Apr 17. Epub 2019 Apr 17.

Korea Brain Research Institute, Department of Neural Development and Disease, 61, Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea. Electronic address:

The most prominent hallmarks of many neurodegenerative diseases are the accumulation of misfolded protein aggregates and the death of certain neuronal populations. Autophagy is the major intracellular mechanism that degrades protein aggregates and damaged cellular components. Many studies have reported that the dysfunction of autophagy is associated with several neurodegenerative diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.04.088DOI Listing

Episodic memory and learning rates in amyotrophic lateral sclerosis without dementia.

Cortex 2019 Mar 19;117:257-265. Epub 2019 Mar 19.

Neurodegenerative Disease Unit, Department of Clinical Research in Neurology, University of Bari "Aldo Moro", Lecce, Italy; Neurodegenerative Disease Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy. Electronic address:

In amyotrophic lateral sclerosis (ALS), memory deficits may be primary or secondary to executive dysfunction. We assessed episodic memory and executive function of nondemented ALS patients, comparing episodic memory profiles and learning rates of ALS patients with those of mild cognitive impairment (MCI) subjects and cognitively healthy controls (HC). In a multidisciplinary tertiary centre for motor neuron disease, 72 nondemented ALS patients, 57 amnestic MCI (aMCI), 89 single non amnestic MCI with compromised executive functions (dysexecutive MCI), and 190 HC were enrolled. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00109452193010
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http://dx.doi.org/10.1016/j.cortex.2019.03.003DOI Listing
March 2019
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Motor cortex metabolite alterations in Amyotrophic Lateral Sclerosis assessed in vivo using edited and non-edited magnetic resonance spectroscopy.

Brain Res 2019 Apr 16. Epub 2019 Apr 16.

Biomedical MRI unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. Electronic address:

Previous MRI and proton spectroscopy (H-MRS) studies have revealed impaired neuronal integrity and altered neurometabolite concentrations in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Here, we aim to use MRI with conventional and novel MRS sequences to further investigate neurometabolic changes in the motor cortex of ALS patients and their relation to clinical parameters. We utilized the novel HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy) MRS sequence to simultaneously quantify the inhibitory neurotransmitter GABA and antioxidant glutathione in ALS patients (n=7) and healthy controls (n=7). Read More

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http://dx.doi.org/10.1016/j.brainres.2019.04.018DOI Listing

White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis.

Neuropathol Appl Neurobiol 2019 Apr 19. Epub 2019 Apr 19.

Department of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.

Objective: The aim of this study was to test the hypothesis that white matter degeneration of the perforant path - as part of the Papez circuit - is a key feature of amyotrophic lateral sclerosis (ALS), even in the absence of frontotemporal dementia (FTD) or deposition of pTDP-43 inclusions in hippocampal granule cells.

Methods: We used diffusion MRI (dMRI), polarized light imaging (PLI) and immunohistochemical analysis of post-mortem hippocampus specimens from controls (n=5) and ALS patients (n=14) to study white matter degeneration in the perforant path.

Results: dMRI demonstrated a decrease in fractional anisotropy (p=0. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/nan.12555
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http://dx.doi.org/10.1111/nan.12555DOI Listing
April 2019
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Frontal Anatomical Correlates of Cognitive and Speech Motor Deficits in Amyotrophic Lateral Sclerosis.

Behav Neurol 2019 13;2019:9518309. Epub 2019 Mar 13.

Sunnybrook Research Institute, Hurvitz Brain Sciences Program, Toronto, Canada.

The goal of this study was to identify neurostructural frontal lobe correlates of cognitive and speaking rate changes in amyotrophic lateral sclerosis (ALS). 17 patients diagnosed with ALS and 12 matched controls underwent clinical, bulbar, and neuropsychological assessment and structural neuroimaging. Neuropsychological testing was performed via a novel computerized frontal battery (ALS-CFB), based on a validated theoretical model of frontal lobe functions, and focused on testing energization, executive function, emotion processing, theory of mind, and behavioral inhibition via antisaccades. Read More

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http://dx.doi.org/10.1155/2019/9518309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436339PMC

Biomarkers in Motor Neuron Disease: A State of the Art Review.

Front Neurol 2019 3;10:291. Epub 2019 Apr 3.

Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom.

Motor neuron disease can be viewed as an umbrella term describing a heterogeneous group of conditions, all of which are relentlessly progressive and ultimately fatal. The average life expectancy is 2 years, but with a broad range of months to decades. Biomarker research deepens disease understanding through exploration of pathophysiological mechanisms which, in turn, highlights targets for novel therapies. Read More

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https://www.frontiersin.org/article/10.3389/fneur.2019.00291
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http://dx.doi.org/10.3389/fneur.2019.00291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456669PMC
April 2019
1 Read

Gene-Environment-Time Interactions in Neurodegenerative Diseases: Hypotheses and Research Approaches.

Ann Neurosci 2018 Dec 4;25(4):261-267. Epub 2018 Dec 4.

Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.

Background: Amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's diseases are age-related neurodegenerative diseases. ALS is not a single entity but a syndrome with many different causes. In all 3 diseases, gene mutations account for only 10-15% of cases. Read More

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https://www.karger.com/Article/FullText/495321
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http://dx.doi.org/10.1159/000495321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470336PMC
December 2018
1 Read

Permittivity of ex vivo healthy and diseased murine skeletal muscle from 10 kHz to 1 MHz.

Sci Data 2019 Apr 18;6(1):37. Epub 2019 Apr 18.

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.

A better understanding of the permittivity property of skeletal muscle is essential for the development of new diagnostic tools and approaches for neuromuscular evaluation. However, there remain important knowledge gaps in our understanding of this property in healthy and diseased skeletal muscle, which hinder its translation into clinical application. Here, we report the permittivity of gastrocnemius muscle in healthy wild type mice and murine models of spinal muscular atrophy, muscular dystrophy, diabetes, amyotrophic lateral sclerosis and in a model of myofiber hypertrophy. Read More

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http://www.nature.com/articles/s41597-019-0045-2
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http://dx.doi.org/10.1038/s41597-019-0045-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472406PMC
April 2019
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Predicting respiratory failure in amyotrophic lateral sclerosis: recruiting a few good pulmonologists.

Authors:
Noah Lechtzin

Eur Respir J 2019 Apr 18;53(4). Epub 2019 Apr 18.

Dept of Medicine, Division of Pulmonary, Critical Care and Sleep, Johns Hopkins University School of Medicine, Baltimore, MD, USA

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http://erj.ersjournals.com/lookup/doi/10.1183/13993003.00360
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http://dx.doi.org/10.1183/13993003.00360-2019DOI Listing
April 2019
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Upper Airway Video Endoscopy: Assessment of the response to positive pressure ventilation and mechanical in-exsufflation.

Pulmonology 2019 Apr 15. Epub 2019 Apr 15.

Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

Upper airways (UA) include the nasal cavities, pharynx, and larynx, and its main function is to warm and filter the inspired air. UA dysfunction is in the pathogenesis of various disorders, such as obstructive sleep apnea syndrome (OSAS) and vocal cord dysfunction. In addition, in some neurodegenerative diseases (e. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S25310437193004
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http://dx.doi.org/10.1016/j.pulmoe.2019.02.008DOI Listing
April 2019
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Coexistence of variants in TBK1 and in other ALS-related genes elucidates an oligogenic model of pathogenesis in sporadic ALS.

Neurobiol Aging 2019 Mar 27. Epub 2019 Mar 27.

Centro Clinico NEMO, Roma, Italy; Dipartimento Scienze dell'invecchiamento, Neurologiche, Ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Neurologia, Roma, Italy; Università Cattolica del Sacro Cuore, Istituto di Neurologia, Roma, Italy. Electronic address:

Variants in tank-binding kinase 1 (TBK1) are responsible for a significant proportion of amyotrophic lateral sclerosis (ALS) cases. In the present study, we analyzed variants in TBK1 extracted by targeted sequencing of 32 genes in a group of 406 Italian patients with ALS. We identified 7 different TBK1 variants in 7 sporadic cases, resulting in a frequency of 1. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.03.010DOI Listing

A Dynamic Bayesian Network model for the simulation of Amyotrophic Lateral Sclerosis progression.

BMC Bioinformatics 2019 Apr 18;20(Suppl 4):118. Epub 2019 Apr 18.

Department of Information Engineering, University of Padova, Gradenigo 6/b, 35131, Padova, Italy.

Background: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease progressively affecting upper and lower motor neurons in the brain and spinal cord. Mean life expectancy is three to five years, with paralysis of muscles, respiratory failure and loss of vital functions being the common causes of death. Clinical manifestations of ALS are heterogeneous due to the mix of anatomic regions involvement and the variability in disease course; consequently, diagnosis and prognosis at the level of individual patient is really challenging. Read More

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http://dx.doi.org/10.1186/s12859-019-2692-xDOI Listing

[Chronic phosphoproteomic in temporal lobe epilepsy mouse models induced by kainic acid].

Beijing Da Xue Xue Bao Yi Xue Ban 2019 Apr;51(2):197-205

Institute of Systems Biomedicine, State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Science, Beijing 100191, China.

Objective: To investigate functions of proteins and signaling pathways involved in epileptogenesis during the chronic stage of temporal lobe epilepsy in mouse models.

Methods: Kainic acid-induced temporal lobe epilepsy models were conducted, when reaching stage 4 using racine scale, the mice of experimental group were supposed to be successfully established. Pentobarbital sodium was injected to stop epileptic seizure in case of death. Read More

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April 2019
3 Reads

Nobiletin Protects Against Systemic Inflammation-Stimulated Memory Impairment via MAPK and NF-κB Signaling Pathways.

J Agric Food Chem 2019 Apr 17. Epub 2019 Apr 17.

Neuroinflammation is intensively demonstrated to be related with various neurodegenerative diseases including Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and Alzheimer disease (AD). As a natural polymethoxylated flavone, Nobiletin (NOB) is reported to alleviate oxidative stress, insulin resistance, and obesity. In this study, we evaluated the protection effects of NOB on neuroinflammation and memory deficit. Read More

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http://dx.doi.org/10.1021/acs.jafc.9b00133DOI Listing
April 2019
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Misfolded SOD1 inclusions in patients with mutations in and other ALS/FTD-associated genes.

J Neurol Neurosurg Psychiatry 2019 Apr 16. Epub 2019 Apr 16.

Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden

Objective: A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in () are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.

Methods: A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue. Read More

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http://jnnp.bmj.com/lookup/doi/10.1136/jnnp-2018-319386
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http://dx.doi.org/10.1136/jnnp-2018-319386DOI Listing
April 2019
2 Reads

Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion.

Hum Genomics 2019 Apr 16;13(1):19. Epub 2019 Apr 16.

Center for Human Disease Modeling, Duke University Medical Center, Carmichael Building, 300 North Duke Street, Suite 48-118, Durham, NC, 27701, USA.

Background: Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases.

Results: We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Read More

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http://dx.doi.org/10.1186/s40246-019-0203-9DOI Listing
April 2019
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Real-Time Performance of a Tactile Neuroprosthesis on Awake Behaving Rats.

IEEE Trans Neural Syst Rehabil Eng 2019 Apr 11. Epub 2019 Apr 11.

With the advancement of electrode and equipment technology, neuroprosthetics have become a promising alternative to partially compensate for the loss of sensorimotor function in amputees and patients with neurological diseases. Cortical neural interfaces are suitable especially for spinal cord injuries and amyotrophic lateral sclerosis. Although considerable success has been achieved in the literature by spike decoding of motor signáis from the human brain, somatosensory feedback is essential for better motor control, interaction with objects, and the embodiment of prosthetic devices. Read More

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https://ieeexplore.ieee.org/document/8688479/
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http://dx.doi.org/10.1109/TNSRE.2019.2910320DOI Listing
April 2019
2 Reads

Prognostic analysis of amyotrophic lateral sclerosis based on clinical features and plasma surface-enhanced Raman spectroscopy.

J Biophotonics 2019 Apr 15:e201900012. Epub 2019 Apr 15.

Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a wide range of survival times. We aimed to explore prognostic factors related to short survival based on clinical features and plasma metabolic signatures using surface-enhanced Raman spectroscopy (SERS). One hundred and thirty-eight sporadic ALS cases were enrolled serially, including 62 for the short-duration group (≤3 years) and 76 for the long-duration group (>3 years). Read More

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http://dx.doi.org/10.1002/jbio.201900012DOI Listing
April 2019
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Ultrasound in the Diagnosis and Monitoring of Amyotrophic Lateral Sclerosis: A Review.

Muscle Nerve 2019 Apr 16. Epub 2019 Apr 16.

Department of Neurology, Penn State Hershey Medical Center, Hershey, PA.

Neuromuscular ultrasound is complementary to electrodiagnostic (EDx) testing and is useful in enhancing the diagnosis of mononeuropathies, peripheral nerve trauma and demyelinating polyneuropathies. There is increasing interest in using ultrasound both to aid in the diagnosis of amyotrophic lateral sclerosis (ALS) and to monitor its progression. In this review, the relevant literature on ultrasound in ALS is reviewed. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.26487
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http://dx.doi.org/10.1002/mus.26487DOI Listing
April 2019
3 Reads

Microstructural correlates of Edinburgh Cognitive and Behavioural ALS Screen (ECAS) changes in amyotrophic lateral sclerosis.

Psychiatry Res Neuroimaging 2019 Apr 2. Epub 2019 Apr 2.

Department of Psychology, University of Campania "Luigi Vanvitelli", Caserta, Italy.

Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was designed for testing patients with amyotrophic lateral sclerosis (ALS), a multi-system neurodegenerative disease characterized by progressive physical disability. In this study, we aim to explore the potential brain microstructural substrates associated with performance on ECAS in the early stages of ALS, using a whole-brain tract-based spatial statistics diffusion tensor imaging approach. Thirty-six non-demented ALS patients, assessed using ECAS, and 35 age-, sex- and education-matched healthy controls underwent magnetic resonance imaging at 3 Tesla. Read More

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http://dx.doi.org/10.1016/j.pscychresns.2019.04.001DOI Listing
April 2019
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Codelivery of Plasmid and Curcumin with Mesoporous Silica Nanoparticles for Promoting Neurite Outgrowth.

ACS Appl Mater Interfaces 2019 Apr 19. Epub 2019 Apr 19.

Department of Chemistry , National Taiwan University , Taipei 106 , Taiwan.

Reactive oxygen species (ROS)-induced oxidative stress leads to neuron damage and is involved in the pathogenesis of chronic inflammation in neurodegenerative diseases (NDs), such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Researchers, therefore, are looking for antiinflammatory drugs and gene therapy approaches to slow down or even prevent neurological disorders. Combining therapeutics has shown a synergistic effect in the treatment of human diseases. Read More

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http://dx.doi.org/10.1021/acsami.9b02797DOI Listing
April 2019
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Rare variants in MYH15 modify amyotrophic lateral sclerosis risk.

Hum Mol Genet 2019 Apr 1. Epub 2019 Apr 1.

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive muscular atrophy and respiratory failure. The G4C2 repeat expansion in the C9orf72 gene is the most prevalent genetic risk for ALS. Mutation carriers (C9ALS) display variability in phenotypes such as age-at-onset and duration, suggesting the existence of additional genetic factors. Read More

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http://dx.doi.org/10.1093/hmg/ddz063DOI Listing

The O-GlcNAc modification protects against protein misfolding and aggregation in neurodegenerative disease.

ACS Chem Neurosci 2019 Apr 15. Epub 2019 Apr 15.

Post-translational modifications (PTM) of proteins are becoming the focus of intense research due to their implications in a broad spectrum of neurodegenerative diseases. Various PTMs have been identified to alter the toxic profiles of proteins which play critical roles in disease etiology. In Alzheimer's disease (AD), dysregulated phosphorylation is reported to promote pathogenic processing of the microtubule-associated tau protein. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00143DOI Listing
April 2019
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RNA Sequencing Reveals Small and Variable Contributions of Infectious Agents to Transcriptomes of Postmortem Nervous Tissues From Amyotrophic Lateral Sclerosis, Alzheimer's Disease and Parkinson's Disease Subjects, and Increased Expression of Genes From Disease-Activated Microglia.

Front Neurosci 2019 28;13:235. Epub 2019 Mar 28.

Parkinson's and Movement Disorders Center, Virginia Commonwealth University, Richmond, VA, United States.

Nervous tissues from both humans with neurodegenerative diseases (NDD) and animals with genetic models of human NDD, such as rare monogenic causes of Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), show activated microglia, suggesting a potential causal role for inflammation in pathogenesis of NDD. We performed paired-end (PE) RNA sequencing (RNA seq) of total RNA's extracted from frozen sections of cervical spinal cords from ALS and CTL subjects, frontal cortical gray matter ribbons of AD and CTL subjects, and ventral midbrains of PD and CTL subjects. Trimmed PE reads were aligned against the hg38 human transcriptome using Tophat2/Bowtie2 (ALS) or HISAT2 (AD and PD) and quantitated with Cufflinks. Read More

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http://dx.doi.org/10.3389/fnins.2019.00235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447612PMC
March 2019
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Can we turn mice into men?: An Editorial for 'Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: a systematic review and meta-analysis' page 284.

Authors:
Albert C Ludolph

J Neurochem 2019 Apr;149(2):168-169

Department of Neurology, University of Ulm, Ulm, Germany.

The pressure to develop pharmacological therapeutic interventions in the field of the rapidly progressing, fatal disease amyotrophic lateral sclerosis (ALS) is traditionally high. Cannabinoids have been discussed for decades as potential neuroprotective agents for ALS because of their antiexcitatory, anti-inflammatory, antiapoptotic and anticatabolic properties. This Editorial highlights a study by Urbi et al in the current issue of the Journal of Neurochemistry, in which the authors performed a Systematic Review and come to the conclusion that cannabinoids seem to have a small, but consistent effect on survival and function of the G93A mice, a standard model for ALS. Read More

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http://dx.doi.org/10.1111/jnc.14651DOI Listing
April 2019
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ALS-Linked Mutations Affect UBQLN2 Oligomerization and Phase Separation in a Position- and Amino Acid-Dependent Manner.

Structure 2019 Apr 4. Epub 2019 Apr 4.

Departments of Biology and Chemistry, Syracuse University, Syracuse, NY 13244, USA; Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY 13244, USA. Electronic address:

Proteasomal shuttle factor UBQLN2 is recruited to stress granules and undergoes liquid-liquid phase separation (LLPS) into protein-containing droplets. Mutations to UBQLN2 have recently been shown to cause dominant X-linked inheritance of amyotrophic lateral sclerosis (ALS) and ALS/dementia. Interestingly, most of these UBQLN2 mutations reside in its proline-rich (Pxx) region, an important modulator of LLPS. Read More

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http://dx.doi.org/10.1016/j.str.2019.03.012DOI Listing
April 2019
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Post-hoc analyses of the edaravone clinical trials Study 16 and Study 19: a step toward more efficient clinical trial designs in amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Apr 13:1-11. Epub 2019 Apr 13.

c Mitsubishi Tanabe Pharma America , Jersey City , NJ , USA , and.

Objectives: The edaravone development program established a study design in which a treatment effect slowing functional loss in amyotrophic lateral sclerosis (ALS) could be documented within a 24-week time frame. This report elucidates the strategic enrichment design utilized to create efficiency and precision in the development program.

Methods: Post-hoc analyses describe learning, sequential iteration, and evolution in study design. Read More

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http://dx.doi.org/10.1080/21678421.2019.1599955DOI Listing
April 2019
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C9orf72 Poly(PR) Dipeptide Repeats Disturb Biomolecular Phase Separation and Disrupt Nucleolar Function.

Mol Cell 2019 Apr 3. Epub 2019 Apr 3.

Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, TN 38105, USA. Electronic address:

Repeat expansion in the C9orf72 gene is the most common cause of the neurodegenerative disorder amyotrophic lateral sclerosis (C9-ALS) and is linked to the unconventional translation of five dipeptide-repeat polypeptides (DPRs). The two enriched in arginine, poly(GR) and poly(PR), infiltrate liquid-like nucleoli, co-localize with the nucleolar protein nucleophosmin (NPM1), and alter the phase separation behavior of NPM1 in vitro. Here, we show that poly(PR) DPRs bind tightly to a long acidic tract within the intrinsically disordered region of NPM1, altering its phase separation with nucleolar partners to the extreme of forming large, soluble complexes that cause droplet dissolution in vitro. Read More

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http://dx.doi.org/10.1016/j.molcel.2019.03.019DOI Listing
April 2019
2 Reads

Molecular dynamics study of structure, folding, and aggregation of poly-glycine-alanine (Poly-GA).

J Chem Phys 2019 Apr;150(14):144307

Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-1211, USA.

Poly-glycine-alanine (poly-GA) proteins are widely believed to be one of the main toxic dipeptide repeat molecules associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia diseases. Using discontinuous molecular dynamics simulation and an all-atom model of the proteins, we study folding, stability, and aggregation of poly-GA. The results demonstrate that poly-GA is an aggregation-prone protein that, after a long enough time, forms β-sheet-rich aggregates that match recent experiment data and that two unique helical structures are formed very frequently, namely, β-helix and double-helix. Read More

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http://dx.doi.org/10.1063/1.5081867DOI Listing
April 2019
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The potential roles of aquaporin 4 in amyotrophic lateral sclerosis.

Neurol Sci 2019 Apr 13. Epub 2019 Apr 13.

Computer Center, The Second Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian, 116023, China.

Aquaporin 4 (AQP4) is a primary water channel found on astrocytes in the central nervous system (CNS). Besides its function in water and ion homeostasis, AQP4 has also been documented to be involved in a myriad of acute and chronic cerebral pathologies, including autoimmune neurodegenerative diseases. AQP4 has been postulated to be associated with the incidence of a progressive neurodegenerative disorder known as amyotrophic lateral sclerosis (ALS), a disease that targets the motor neurons, causing muscle weakness and eventually paralysis. Read More

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http://link.springer.com/10.1007/s10072-019-03877-5
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http://dx.doi.org/10.1007/s10072-019-03877-5DOI Listing
April 2019
2 Reads

The role of the protein-RNA recognition code in neurodegeneration.

Authors:
Jozef Nahalka

Cell Mol Life Sci 2019 Apr 12. Epub 2019 Apr 12.

Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dubravska cesta 9, 84538, Bratislava, Slovak Republic.

MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post-translational riboregulation. This conceptual review explores the literature on neurodegenerative disorders. Read More

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http://dx.doi.org/10.1007/s00018-019-03096-3DOI Listing
April 2019
3 Reads

ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97.

Mol Cell 2019 Apr 3. Epub 2019 Apr 3.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address:

Disturbances in autophagy and stress granule dynamics have been implicated as potential mechanisms underlying inclusion body myopathy (IBM) and related disorders. Yet the roles of core autophagy proteins in IBM and stress granule dynamics remain poorly characterized. Here, we demonstrate that disrupted expression of the core autophagy proteins ULK1 and ULK2 in mice causes a vacuolar myopathy with ubiquitin and TDP-43-positive inclusions; this myopathy is similar to that caused by VCP/p97 mutations, the most common cause of familial IBM. Read More

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http://dx.doi.org/10.1016/j.molcel.2019.03.027DOI Listing
April 2019
1 Read

C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition.

Neurobiol Aging 2019 Mar 11. Epub 2019 Mar 11.

Molecular Neurology, Research Programs Unit, Department of Neurology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.026DOI Listing
March 2019
1 Read

Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS) in Norway: Protocol for validation and a prospective cohort study.

Contemp Clin Trials Commun 2019 Jun 18;14:100347. Epub 2019 Mar 18.

Department of Neurology, Neurologic Clinic, Haukeland University Hospital, Bergen, Norway.

In amyotrophic lateral sclerosis (ALS) cognitive impairment may occur. This could detrimentally influence communication between patient and health-care professionals and make clinical assessment difficult. Given the short life expectancy after diagnosis, it is crucial to accurately identify ALS patients early. Read More

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http://dx.doi.org/10.1016/j.conctc.2019.100347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444026PMC
June 2019
1 Read

Loss of CREST leads to neuroinflammatory responses and ALS-like motor defects in mice.

Transl Neurodegener 2019 2;8:13. Epub 2019 Apr 2.

1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.

Background: Amyotrophic lateral sclerosis (ALS) is a late onset neurodegenerative disease with fast progression. ALS has heavy genetic components in which a series of genetic mutations have been identified. In 2013, Mutations of the gene (also known as ), which functions as a calcium-regulated transcriptional activator, were found in sporadic ALS patients. Read More

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http://dx.doi.org/10.1186/s40035-019-0152-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444434PMC
April 2019
3 Reads

Exome array analysis of rare and low frequency variants in amyotrophic lateral sclerosis.

Sci Rep 2019 Apr 11;9(1):5931. Epub 2019 Apr 11.

Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 individuals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts. Read More

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http://www.nature.com/articles/s41598-019-42091-3
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http://dx.doi.org/10.1038/s41598-019-42091-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459905PMC
April 2019
2 Reads

Excess glutamate secreted from astrocytes drives upregulation of P-glycoprotein in endothelial cells in amyotrophic lateral sclerosis.

Exp Neurol 2019 Apr 9. Epub 2019 Apr 9.

Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA. Electronic address:

In amyotrophic lateral sclerosis (ALS), upregulation in expression and activity of the ABC transporter P-glycoprotein (P-gp) driven by disease advancement progressively reduces CNS penetration and efficacy of the ALS drug, riluzole. Post-mortem spinal cord tissues from ALS patients revealed elevated P-gp expression levels in endothelial cells of the blood-spinal cord barrier compared to levels measured in control, non-diseased individuals. We recently found that astrocytes expressing familial ALS-linked SOD1 mutations regulate expression levels of P-gp in endothelial cells, which also exhibit a concomitant, significant increase in reactive oxygen species production and NFκB nuclear translocation when exposed to mutant SOD1 astrocyte conditioned media. Read More

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http://dx.doi.org/10.1016/j.expneurol.2019.04.002DOI Listing
April 2019
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A Novel Pharyngeal Clearance Maneuver for Initial Tracheostomy Tube Cuff Deflation in High Cervical Tetraplegia.

Am J Phys Med Rehabil 2019 Apr 9. Epub 2019 Apr 9.

Rehabilitation Research Center at Santa Clara Valley Medical Center, San Jose, CA.

Mechanical insufflation-exsufflation (MIE), or "cough-assist" is a commonly used method of clearing tracheal and pulmonary secretions in patients with respiratory insufficiency secondary to spinal cord injury (SCI). This report presents a novel technique termed the Pharyngeal Clearance Maneuver (PCM) which utilizes a modified application of the MIE device to mobilize "secretion burden" at the portion of the trachea above the tracheostomy cuff during cuff deflation. Utilization of this strategy may reduce the risk of aspiration, infection, and respiratory compromise for patients with high cervical SCI in the acute rehabilitation setting. Read More

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http://dx.doi.org/10.1097/PHM.0000000000001192DOI Listing
April 2019
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Air contamination during medical treatment results in deposits of microemboli in the lungs: An autopsy study.

Int J Artif Organs 2019 Apr 11:391398819840363. Epub 2019 Apr 11.

2 Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Umeå, Sweden.

Introduction: Microbubbles of air may enter into patients during conventional hemodialysis, infusions of fluids, or by injections. The aim of this study was to investigate whether the air that enters the patient during hemodialysis can be detected in the lungs after death, and if so, whether this may be related to tissue damage.

Methods: The material consisted of lung tissue from five chronic hemodialysis patients who died either during (two) or after hemodialysis (range 10 min from start until 3333 min after the last hemodialysis session); as reference group tissue was taken from seven patients who died due to amyotrophic lateral sclerosis. Read More

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http://dx.doi.org/10.1177/0391398819840363DOI Listing
April 2019
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Predictors of amyotrophic lateral sclerosis mimic syndrome.

Acta Neurol Belg 2019 Apr 10. Epub 2019 Apr 10.

ALS Clinic, Neurology Department, Hospital Ramos Mejía, Gral. Urquiza 609, Zip 1221 ADC, Buenos Aires, Argentina.

The term amyotrophic lateral sclerosis mimic syndrome (ALSms) includes pathologies that present signs or symptoms similar to those caused by amyotrophic lateral sclerosis (ALS), which can lead to misdiagnosis. In general, any kind of misdiagnosis can result in negative clinical, psychological and economic consequences as well diagnostic and treatment delay. The objectives were to determine the frequency and to compare the demographic and clinical characteristics of patients with ALS and ALSms in our ALS clinic. Read More

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http://dx.doi.org/10.1007/s13760-019-01135-1DOI Listing
April 2019
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ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis.

Front Neurol 2019 27;10:293. Epub 2019 Mar 27.

Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.

Disease-modifying therapies for amyotrophic lateral sclerosis (ALS) are still not satisfactory. The Rho kinase (ROCK) inhibitor fasudil has demonstrated beneficial effects in cell culture and animal models of ALS. For many years, fasudil has been approved in Japan for the treatment of vasospasm in patients with subarachnoid hemorrhage with a favorable safety profile. Read More

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http://dx.doi.org/10.3389/fneur.2019.00293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446974PMC
March 2019
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Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review.

Front Neurosci 2019 26;13:236. Epub 2019 Mar 26.

Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia.

To date, there is no cure or disease-modifying agents available for most well-known neurological disorders. Current therapy is typically focused on relieving symptoms and supportive care in improving the quality of life of affected patients. Furthermore, the traditional drug discovery technique is more challenging, particularly for neurological disorders. Read More

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http://dx.doi.org/10.3389/fnins.2019.00236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444273PMC
March 2019
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Tracheotomy in Amyotrophic Lateral Sclerosis: The Argument in Favor.

Arch Bronconeumol 2019 Apr 7. Epub 2019 Apr 7.

Servicio de Neumología, Hospital Clínico Universitario, Valencia, España; Instituto Investigación Sanitaria INCLIVA, Valencia, España.

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http://dx.doi.org/10.1016/j.arbres.2018.11.007DOI Listing
April 2019
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[Jean-Martin Charcot, discovery and nomenclature of amyotrophic lateral sclerosis].

Authors:
Y L Ma Z P Li

Zhonghua Yi Shi Za Zhi 2019 Jan;49(1):14-18

Department of Medical History, School of Basic Medicine Sciences, Harbin Medical University, Harbin 150086, China.

In the 19th century, neurologists discovered a series of diseases characterized by limb weakness and muscle atrophy, but it was not certain whether they were variants of the same disease or completely different diseases. In 1869, Jean-Martin Charcot first diagnosed the disease, and began to use the term "amyotrophic lateral sclerosis" in 1874. The disease is also known as "Lou Gehrig's disease" in the United States, "Charcot's disease" in France, and "Motor Neuron Disease (MND)" in UK. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0255-7053.2019.01.003DOI Listing
January 2019
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Aberrant Phase Transitions: Side Effects and Novel Therapeutic Strategies in Human Disease.

Front Genet 2019 22;10:173. Epub 2019 Mar 22.

University of Rome "Foro Italico", Rome, Italy.

Phase separation is a physiological process occurring spontaneously when single-phase molecular complexes separate in two phases, a concentrated phase and a more diluted one. Eukaryotic cells employ phase transition strategies to promote the formation of intracellular territories not delimited by membranes with increased local RNA concentration, such as nucleolus, paraspeckles, P granules, Cajal bodies, P-bodies, and stress granules. These organelles contain both proteins and coding and non-coding RNAs and play important roles in different steps of the regulation of gene expression and in cellular signaling. Read More

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http://dx.doi.org/10.3389/fgene.2019.00173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440380PMC
March 2019
2 Reads

Ethical Principles in Patient-Centered Medical Care to Support Quality of Life in Amyotrophic Lateral Sclerosis.

Front Neurol 2019 22;10:259. Epub 2019 Mar 22.

Department of Neurology, University of Ulm, Ulm, Germany.

It is one of the primary goals of medical care to secure good quality of life (QoL) while prolonging survival. This is a major challenge in severe medical conditions with a prognosis such as amyotrophic lateral sclerosis (ALS). Further, the definition of QoL and the question whether survival in this severe condition is compatible with a good QoL is a matter of subjective and culture-specific debate. Read More

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http://dx.doi.org/10.3389/fneur.2019.00259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439311PMC
March 2019
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Small molecule targeting of RNA structures in neurological disorders.

Ann N Y Acad Sci 2019 Apr 9. Epub 2019 Apr 9.

Department of Chemistry, The Scripps Research Institute, Jupiter, Florida.

Aberrant RNA structure and function operate in neurological disease progression and severity. As RNA contributes to disease pathology in a complex fashion, that is, via various mechanisms, it has become an attractive therapeutic target for small molecules and oligonucleotides. In this review, we discuss the identification of RNA structures that cause or contribute to neurological diseases as well as recent progress toward the development of small molecules that target them, including small molecule modulators of pre-mRNA splicing and RNA repeat expansions that cause microsatellite disorders such as Huntington's disease and amyotrophic lateral sclerosis. Read More

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http://dx.doi.org/10.1111/nyas.14051DOI Listing
April 2019
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Targeting Macrophage for the Treatment of Amyotrophic Lateral Sclerosis.

CNS Neurol Disord Drug Targets 2019 Apr 8. Epub 2019 Apr 8.

Translational Center for Stem Cell Research, Tongji Hospital, Stem Cell Research Center, Tongji University School of Medicine, Shanghai. China.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that specifically affects motor neurons in the brain and in the spinal cord. Patients with amyotrophic lateral sclerosis usually die from respiratory failure within 3 to 5 years from when the symptoms first appear. Currently, there is no cure for amyotrophic lateral sclerosis. Read More

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http://dx.doi.org/10.2174/1871527318666190409103831DOI Listing
April 2019
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Plasma creatinine and amyotrophic lateral sclerosis prognosis: a systematic review and meta-analysis.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Apr 9:1-8. Epub 2019 Apr 9.

a UMR 1253, Team 2, INSERM/University of Tours , Tours , France and.

Background: Plasma creatinine has been described as a prognostic biomarker for Amyotrophic Lateral Sclerosis (ALS), but with conflicting results in the literature. We performed a systematic review followed by a meta-analysis to address this question.

Methods: We performed a systematic review of Pubmed, Embase and Cochrane databases and retrieved 14 distinct cohorts (19 studies) reporting results regarding the relationship between plasma creatinine and a clinical marker for ALS progression, notably ALSFRS (ALS Functional Rating Scale) and survival. Read More

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http://dx.doi.org/10.1080/21678421.2019.1572192DOI Listing
April 2019
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Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models.

J Vis Exp 2019 Mar 24(145). Epub 2019 Mar 24.

Chemistry Department, Brooklyn College; Ph.D. Programs in Chemistry, Biochemistry, and Biology, Graduate Center of the City University of New York;

Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), cause the loss of hundreds of thousands of lives each year. Effective treatment options able to halt disease progression are lacking. Despite the extensive sequencing efforts in large patient populations, the majority of ALS and PD cases remain unexplained by genetic mutations alone. Read More

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http://dx.doi.org/10.3791/59104DOI Listing
March 2019
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