33,866 results match your criteria Primary Lateral Sclerosis


Nanovehicles for co-delivery of anticancer agents.

Drug Discov Today 2020 Jul 2. Epub 2020 Jul 2.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa. Electronic address:

Effective cancer treatment remains a significant challenge in human healthcare. Although many different types of cancer therapy have been tested, scientists have now concluded that combinations of drugs, or drugs plus gene therapy, can target multiple pathways to fight cancer. Nanovehicles can increase drug uptake inside tumor cells, improve biodistribution and accumulation at tumor sites. Read More

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http://dx.doi.org/10.1016/j.drudis.2020.06.027DOI Listing

FABP7 upregulation induces a neurotoxic phenotype in astrocytes.

Glia 2020 Jul 3. Epub 2020 Jul 3.

Department of Neurology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Fatty acid binding proteins (FABPs) are key regulators of lipid metabolism, energy homeostasis, and inflammation. They participate in fatty acid metabolism by regulating their uptake, transport, and availability of ligands to nuclear receptors. In the adult brain, FABP7 is especially abundant in astrocytes that are rich in cytoplasmic granules originated from damaged mitochondria. Read More

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http://dx.doi.org/10.1002/glia.23879DOI Listing

Quantitative patterns of motor cortex proteinopathy across ALS genotypes.

Acta Neuropathol Commun 2020 Jul 2;8(1):98. Epub 2020 Jul 2.

Nuffield Department of Clinical Neurosciences, University of Oxford, Level 1, West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK.

Degeneration of the primary motor cortex is a defining feature of amyotrophic lateral sclerosis (ALS), which is associated with the accumulation of microscopic protein aggregates in neurons and glia. However, little is known about the quantitative burden and pattern of motor cortex proteinopathies across ALS genotypes. We combined quantitative digital image analysis with multi-level generalized linear modelling in an independent cohort of 82 ALS cases to explore the relationship between genotype, total proteinopathy load and cellular vulnerability to aggregate formation. Read More

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http://dx.doi.org/10.1186/s40478-020-00961-2DOI Listing

Standardized reporter systems for purification and imaging of human pluripotent stem cell-derived motor neurons and other cholinergic cells.

Neuroscience 2020 Jun 29. Epub 2020 Jun 29.

Departments of Pathology and Cell Biology, Neuroscience, Rehabilitation and Regenerative Medicine (in Neurology), Columbia University Irving Medical Center, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:

Reliable and consistent pluripotent stem cell reporter systems for efficient purification and visualization of motor neurons are essential reagents for the study of normal motor neuron biology and for effective disease modeling. To overcome the inherent noisiness of transgene-based reporters, we developed a new series of human induced pluripotent stem cell lines by knocking in tdTomato, Cre, or CreERT2 recombinase into the HB9 (MNX1) or VACHT (SLC18A3) genomic loci. The new lines were validated by directed differentiation into spinal motor neurons and immunostaining for motor neuron markers HB9 and ISL1. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2020.06.028DOI Listing

Nusinersen ameliorates motor function and prevents motoneuron Cajal body disassembly and abnormal poly(A) RNA distribution in a SMA mouse model.

Sci Rep 2020 Jul 1;10(1):10738. Epub 2020 Jul 1.

"Instituto de Investigación Marqués de Valdecilla" (IDIVAL), Santander, Spain.

Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease characterized by degeneration of spinal cord alpha motor neurons (αMNs). SMA is caused by the homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene, resulting in reduced expression of SMN protein, which leads to αMN degeneration and muscle atrophy. The majority of transcripts of a second gene (SMN2) generate an alternative spliced isoform that lacks exon 7 and produces a truncated nonfunctional form of SMN. Read More

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http://dx.doi.org/10.1038/s41598-020-67569-3DOI Listing

[Consideration of Advanced Pharmaceutical Control Functions through Pharmacy-provided Home Pharmaceutical Care].

Authors:
Masahiko Kimura

Yakugaku Zasshi 2020 ;140(7):841-850

Akebono Pharmacy.

In October 2015, the Ministry of Health, Labour and Welfare of Japan newly included "health support functions" and "advanced pharmaceutical control functions" as part of "primary-care pharmacy" in the pharmacy vision for patients. "Health support functions" were defined as recommending that patients seek medical consultations, introducing them to relevant medical institutions, and contributing to disease prevention and health support among local residents, apart from health counseling and the consolidation of a framework for the appropriate selection and supply of and advice on pharmacist-only over-the-counter medications, etc. On the other hand, the term "advanced pharmaceutical control functions" is presumed to imply meeting the needs for advanced pharmaceutical control, e. Read More

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http://dx.doi.org/10.1248/yakushi.19-00237-1DOI Listing
January 2020

A Systematic Review of Genotype-Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS.

J Pers Med 2020 Jun 29;10(3). Epub 2020 Jun 29.

Northern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry BT47 6SB, Northern Ireland, UK.

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. Read More

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http://dx.doi.org/10.3390/jpm10030058DOI Listing

Neuronal RNA-binding protein dysfunction in multiple sclerosis cortex.

Ann Clin Transl Neurol 2020 Jul 1. Epub 2020 Jul 1.

Department of Anatomy, Physiology and Pharmacology & Cameco MS Neuroscience Research Center, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

Objective: Neurodegeneration is thought to be the primary cause of neurological disability in multiple sclerosis (MS). Dysfunctional RNA-binding proteins (RBPs) including their mislocalization from nucleus to cytoplasm, stress granule formation, and altered RNA metabolism have been found to underlie neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia. Yet, little is known about the role of dysfunctional RBPs in the pathogenesis of neurodegeneration in MS. Read More

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http://dx.doi.org/10.1002/acn3.51103DOI Listing

Dietary Amino Acids Impact LRRK2-induced Neurodegeneration in Parkinson's Disease Models.

J Neurosci 2020 Jun 30. Epub 2020 Jun 30.

Jungers Center for Neurosciences Research, Department of Neurology

The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of Parkinson's disease (PD) and results in age-related dopamine neuron loss and locomotor dysfunction in through an aberrant increase in bulk neuronal protein synthesis. Under non-pathologic conditions, protein synthesis is tightly controlled by metabolic regulation. Whether nutritional and metabolic influences on protein synthesis can modulate the pathogenic effect of LRRK2 on protein synthesis and thereby impact neuronal loss is a key unresolved question. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.2809-19.2020DOI Listing

Optimized Protocol to Generate Spinal Motor Neuron Cells from Induced Pluripotent Stem Cells from Charcot Marie Tooth Patients.

Brain Sci 2020 Jun 27;10(7). Epub 2020 Jun 27.

CHU de Limoges, Service de Biochimie et Génétique Moléculaire, F-87000 Limoges, France.

Modelling rare neurogenetic diseases to develop new therapeutic strategies is highly challenging. The use of human-induced pluripotent stem cells (hiPSCs) is a powerful approach to obtain specialized cells from patients. For hereditary peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) Type II, spinal motor neurons (MNs) are impaired but are very difficult to study. Read More

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http://dx.doi.org/10.3390/brainsci10070407DOI Listing

Mechanism of Action of OnabotulinumtoxinA in Chronic Migraine: A Narrative Review.

Headache 2020 Jun 30. Epub 2020 Jun 30.

Allergan, Inc., Irvine, CA, USA.

Objective: To review the literature on the mechanism of action of onabotulinumtoxinA in chronic migraine.

Background: OnabotulinumtoxinA is a chronic migraine preventive treatment that significantly reduces headache frequency. The traditional mechanism described for onabotulinumtoxinA - reducing muscle contractions - is insufficient to explain its efficacy in migraine, which is primarily a sensory neurological disease. Read More

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http://dx.doi.org/10.1111/head.13849DOI Listing

Dopamine Depletion induces Neuron-specific Alterations of GABAergic Transmission in the Mouse Striatum.

Eur J Neurosci 2020 Jun 29. Epub 2020 Jun 29.

University of Zurich, Institute of Pharmacology and Toxicology, 8057, Zurich, Switzerland.

Lack of dopamine (DA) in the striatum and the consequential dysregulation of thalamo-cortical circuits are major causes of motor impairments in Parkinson's disease. The striatum receives multiple cortical and subcortical afferents. Its role in movement control and motor skills learning is regulated by DA from the nigro-striatal pathway. Read More

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http://dx.doi.org/10.1111/ejn.14886DOI Listing

Excellent reliability of the ALSFRS-R administered via videoconferencing: A study of people with motor neuron disease in Scotland.

J Neurol Sci 2020 Jun 21;416:116991. Epub 2020 Jun 21.

Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK; Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK; Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, UK. Electronic address:

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http://dx.doi.org/10.1016/j.jns.2020.116991DOI Listing

Microglia in Motor Neuron Disease.

Neuropathol Appl Neurobiol 2020 Jun 28. Epub 2020 Jun 28.

University of Sheffield, Sheffield, UK.

Motor Neuron Disease (MND) is a fatal neurodegenerative condition, which is characterised by the selective loss of the upper and lower motor neurons. At the sites of motor neuron injury, accumulation of activated microglia, the primary immune cells of the central nervous system, are commonly observed in both human post-mortem studies and animal models of MND. Microglial activation has been found to correlate with many clinical features and importantly, the speed of disease progression in humans. Read More

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http://dx.doi.org/10.1111/nan.12640DOI Listing

Central motor conduction time reveals upper motor neuron involvement masked by lower motor neuron impairment in a significant portion of patients with amyotrophic lateral sclerosis.

Clin Neurophysiol 2020 Jun 12;131(8):1896-1901. Epub 2020 Jun 12.

Department of Neurology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Japan; Department of Human Neurophysiology, Fukushima Medical University, 1 Hikarigaoka, Fukusima, Japan.

Objective: We retrospectively investigated the utility of the central motor conduction time (CMCT) in detecting upper motor neuron (UMN) involvements in patients with amyotrophic lateral sclerosis (ALS).

Methods: Fifty-two ALS patients and 12 disease control patients participated in this study. Surface electromyograms were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Read More

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http://dx.doi.org/10.1016/j.clinph.2020.05.021DOI Listing

Relations of clinical symptoms with dopamine transporter imaging in drug-naïve Parkinson's disease.

Clin Neurol Neurosurg 2020 May 26;196:105960. Epub 2020 May 26.

Department of Neurology, Brain Science Center, Sapporo City General Hospital, Kita 11-nishi 13, Chuo Ku, Sapporo, Hokkaido 060-8604, Japan.

Objectives: The aim of the present study was to determine the relations of clinical symptoms with nigrostriatal neuron loss in drug-naïve patients with Parkinson's disease (PD). We examined the severity of motor symptoms and freezing of gait (FOG), falls and overactive bladder (OAB) in PD patients and their relations with striatal dopamine transporter (DAT) binding.

Patients And Methods: Thirty-two untreated PD patients (14 men and 18 women with a mean age of 71. Read More

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http://dx.doi.org/10.1016/j.clineuro.2020.105960DOI Listing

PCL/gelatin scaffolds and BETA-BOSWELLIC ACID (BBA) synergistically increase the efficiency of CGR8 stem cells differentiation into dopaminergic neuron: A new paradigm of Parkinson's disease cell therapy.

J Biomed Mater Res A 2020 Jun 25. Epub 2020 Jun 25.

Brain and Spinal Cord Injury Research Center (BASIR), Tehran University of Medical Sciences, Tehran, Iran.

Parkinson's disease is a progressive degenerative disorder in the central nervous system (CNS), which is distinguished by the death of dopamine producing nerve cells. Levodopa, a dopamine precursor drug, is the current standard of care of symptomatic treatment for Parkinson's disease. However, the long-term use of the drug is associated with the development of motor fluctuations and dyskinesias. Read More

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http://dx.doi.org/10.1002/jbm.a.37040DOI Listing

Absence of subcerebral projection neurons is beneficial in a mouse model of ALS.

Ann Neurol 2020 Jun 26. Epub 2020 Jun 26.

Inserm UMR_S 1118, Mécanismes centraux et périphériques de la neurodégénérescence, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.

Objective: Recent studies carried on amyotrophic lateral sclerosis patients suggest that the disease may initiate in the motor cortex and spread to its targets along the corticofugal tracts. In this study, we aimed at experimentally testing the corticofugal hypothesis of amyotrophic lateral sclerosis.

Methods: Sod1 and Fezf2 knockout mouse lines were crossed to generate a model that ubiquitously expresses a mutant of the murine Sod1 gene, a condition sufficient to induce progressive motor symptoms and premature death, but genetically lacks corticospinal neurons and other subcerebral projection neurons, one of the main populations of corticofugal neurons. Read More

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http://dx.doi.org/10.1002/ana.25833DOI Listing

Efficacy of Botulinum Toxin for Treating Sialorrhea in Neuromuscular Conditions.

Front Neurol 2020 10;11:513. Epub 2020 Jun 10.

Assistant Professor of Neurology, Department of Neurology, University of Missouri, Columbia, MO, United States.

Drooling related to bulbar weakness and dysfunction is a common concern in patients with neuromuscular disease. While there are numerous medications to manage sialorrhea, they are often limited by side effects and lack of efficacy. Botulinum toxin has shown to benefit ALS patients in a few studies, but there is scant data on the benefit in other neuromuscular conditions. Read More

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http://dx.doi.org/10.3389/fneur.2020.00513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297943PMC

Generating ventral spinal organoids from human induced pluripotent stem cells.

Methods Cell Biol 2020 21;159:257-277. Epub 2020 Apr 21.

Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore; Yong Loo Lin School of Medicine (Physiology), National University of Singapore, Singapore; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; National Neuroscience Institute, Singapore. Electronic address:

Current advances in human pluripotent stem cell (hPSC) technology allow directed differentiation into three-dimensional spinal organoid cultures that mimic the unique microenvironment and cytoarchitecture of the human spinal cord. Organoids also serves as important cellular tools to model spinal cord development and motor neuron diseases such as Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis. In this chapter, we describe a detailed step-by-step methodology to generate spinal organoids from human PSCs. Read More

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http://dx.doi.org/10.1016/bs.mcb.2020.03.010DOI Listing

Global alterations to the choroid plexus blood-CSF barrier in amyotrophic lateral sclerosis.

Acta Neuropathol Commun 2020 Jun 26;8(1):92. Epub 2020 Jun 26.

Department of Neurobiology, St. Joseph's Hospital and Medical Center and Barrow Neurological Institute, 350 W Thomas Road, Phoenix, AZ, 85013, USA.

The choroid plexus (CP) is a highly vascularized structure located in the ventricles that forms the blood-CSF barrier (BCSFB) and separates the blood from the cerebrospinal fluid (CSF). In addition to its role as a physical barrier, the CP functions in CSF secretion, transport of nutrients into the central nervous system (CNS) and a gated point of entry of circulating immune cells into the CNS. Aging and neurodegeneration have been reported to affect CP morphology and function and increase protein leakage from blood to the CSF. Read More

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http://dx.doi.org/10.1186/s40478-020-00968-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318439PMC

Understanding and managing metabolic dysfunction in Amyotrophic Lateral Sclerosis.

Expert Rev Neurother 2020 Jun 25. Epub 2020 Jun 25.

Unité INSERM U1253, équipe, neurogénomique et physiopathologie neuronale, Université de Tours , Tours, France.

Introduction Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease that leads to death after a median survival of 36 months. The development of an effective treatment has proven to be extremely difficult due to the inadequate understanding of the pathogenesis of ALS. Energy metabolism is thoroughly involved in the disease based on the discoveries of hypermetabolism, lipid/glucose metabolism, the tricarboxylic acid (TCA) cycle, and mitochondrial impairment. Read More

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http://dx.doi.org/10.1080/14737175.2020.1788389DOI Listing

Focus on the heterogeneity of amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 25:1-11. Epub 2020 Jun 25.

Mario Negri-ALS Study Group, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.

The clinical manifestations of amyotrophic lateral sclerosis (ALS) are variable in terms of age at disease onset, site of onset, progression of symptoms, motor neuron involvement, and the occurrence of cognitive and behavioral changes. Genetic background is a key determinant of the ALS phenotype. The mortality of the disease also varies with the ancestral origin of the affected population and environmental factors are likely to be associated with ALS at least within some cohorts. Read More

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http://dx.doi.org/10.1080/21678421.2020.1779298DOI Listing
June 2020
2.591 Impact Factor

Therapeutic Approaches Targeting Protein Aggregation in Amyotrophic Lateral Sclerosis.

Front Mol Neurosci 2020 9;13:98. Epub 2020 Jun 9.

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease that targets motor neurons (MNs) in the brain and spinal cord. It leads to gradual loss of motor signals to muscles leading to atrophy and weakness. Most patients do not survive for more than 3-5 years after disease onset. Read More

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http://dx.doi.org/10.3389/fnmol.2020.00098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296057PMC

GSK-3β Contributes to Parkinsonian Dopaminergic Neuron Death: Evidence From Conditional Knockout Mice and Tideglusib.

Front Mol Neurosci 2020 3;13:81. Epub 2020 Jun 3.

Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Glycogen synthase kinase-3 (GSK-3) dysregulation has been implicated in nigral dopaminergic neurodegeneration, one of the main pathological features of Parkinson's disease (PD). The two isoforms, GSK-3α and GSK-3β, have both been suggested to play a detrimental role in neuronal death. To date, several studies have focused on the role of GSK-3β on PD pathogenesis, while the role of GSK-3α has been largely overlooked. Read More

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http://dx.doi.org/10.3389/fnmol.2020.00081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283909PMC

Multi-targeting sodium and calcium channels using venom peptides for the treatment of complex ion channels-related diseases.

Biochem Pharmacol 2020 Jun 21:114107. Epub 2020 Jun 21.

Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Rd, St Lucia, QLD, AU 4072.

Venom peptides are amongst the most exquisite group of bioactive molecules able to alter the normal physiology of organisms. These bioactive peptides penetrate tissues and blood vessels to encounter a number of receptors and ion channels to which they bind with high affinity and execute modulatory activities. Arachnid is the most diverse class of venomous animals often rich in peptides modulating voltage-gated sodium (Na), calcium (Ca), and potassium (K) channels. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114107DOI Listing

MiR-410-3p overexpression ameliorates neurological deficits in rats with hypoxic-ischemic brain damage.

Brain Res Bull 2020 Jun 21. Epub 2020 Jun 21.

Department of Anesthesiology, Department of Neurology, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China; School of Pharmacy and Medical Sciences, Faculty of Health Sciences, University of South Australia, Adelaide, 5000, Australia. Electronic address:

Neonatal hypoxic-ischemic encephalopathy (HIE) is major cause of neonatal death or long-term neurodevelopmental disabilities, which becomes a major practical problem currently in clinic. Whereas, its pathophysiology and underlying molecular mechanism is not clear. MicroRNAs are involved in the normal growth and development of neuronal cells. Read More

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http://dx.doi.org/10.1016/j.brainresbull.2020.06.011DOI Listing

Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database.

Hum Mutat 2020 Jun 24. Epub 2020 Jun 24.

Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Research Center for Translational Medicine (KUTTAM), Koç University School of Medicine, Istanbul, Turkey.

The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. Read More

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http://dx.doi.org/10.1002/humu.24055DOI Listing

Using patient-reported symptoms of dyspnea for screening reduced respiratory function in patients with motor neuron diseases.

J Neurol 2020 Jun 23. Epub 2020 Jun 23.

Department of Rehabilitation, Physical Therapy Science and Sports, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Background: Poor monitoring of respiratory function may lead to late initiation of non-invasive ventilation (NIV) in patients with motor neuron diseases (MND). Monitoring could be improved by remotely assessing hypoventilation symptoms between clinic visits. We aimed to determine which patient-reported hypoventilation symptoms are best for screening reduced respiratory function in patients with MND, and compared them to the respiratory domain of the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). Read More

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http://dx.doi.org/10.1007/s00415-020-10003-5DOI Listing

Tight expression regulation of senataxin, linked to motor neuron disease and ataxia, is required to avert cell-cycle block and nucleolus disassembly.

Heliyon 2020 Jun 13;6(6):e04165. Epub 2020 Jun 13.

Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA.

The Senataxin (SETX) protein exhibits strong sequence conservation with the helicase domain of the yeast protein Sen1p, and recessive mutations cause a severe ataxia, known as Ataxia with Oculomotor Apraxia type 2, while dominant mutations cause Amyotrophic Lateral Sclerosis type 4. SETX is a very low abundance protein, and its expression is tightly regulated, such that large increases in mRNA levels fail to significantly increase protein levels. Despite this, transient transfection in cell culture can boost SETX protein levels on an individual cell basis. Read More

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http://dx.doi.org/10.1016/j.heliyon.2020.e04165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301172PMC

Prognostic value of weight loss in patients with amyotrophic lateral sclerosis.

J Neurol Neurosurg Psychiatry 2020 Jun 23. Epub 2020 Jun 23.

Department of Neurology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.

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http://dx.doi.org/10.1136/jnnp-2020-323440DOI Listing

Prognostic value of weight loss in patients with amyotrophic lateral sclerosis: a population-based study.

J Neurol Neurosurg Psychiatry 2020 Jun 23. Epub 2020 Jun 23.

Neurology, University Medical Centre Utrecht Brain Centre, Utrecht, The Netherlands

Objective: To determine the prevalence and prognostic value of weight loss (WL) prior to diagnosis in patients with amyotrophic lateral sclerosis (ALS).

Methods: We enrolled patients diagnosed with ALS between 2010 and 2018 in a population-based setting. At diagnosis, detailed information was obtained regarding the patient's disease characteristics, anthropological changes, ALS-related genotypes and cognitive functioning. Read More

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http://dx.doi.org/10.1136/jnnp-2020-322909DOI Listing

An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: towards a biomarker for amyotrophic lateral sclerosis/motor neuron disease.

Open Biol 2020 Jun 24;10(6):200116. Epub 2020 Jun 24.

Brain Chemistry Labs, Institute for Ethnomedicine, PO Box 3464, Jackson, WY 83001, USA.

Biomarkers for amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are currently not clinically available for disease diagnosis or analysis of disease progression. If identified, biomarkers could improve patient outcomes by enabling early intervention and assist in the determination of treatment efficacy. We hypothesized that neural-enriched extracellular vesicles could provide microRNA (miRNA) fingerprints with unequivocal signatures of neurodegeneration. Read More

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http://dx.doi.org/10.1098/rsob.200116DOI Listing

Comparative anatomy of the mammalian neuromuscular junction.

J Anat 2020 Jun 23. Epub 2020 Jun 23.

Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh, UK.

The neuromuscular junction (NMJ)-a synapse formed between lower motor neuron and skeletal muscle fibre-represents a major focus of both basic neuroscience research and clinical neuroscience research. Although the NMJ is known to play an important role in many neurodegenerative conditions affecting humans, the vast majority of anatomical and physiological data concerning the NMJ come from lower mammalian (e.g. Read More

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http://dx.doi.org/10.1111/joa.13260DOI Listing

Wide range of reduced penetrance alleles in spinal and bulbar muscular atrophy: a model-based approach.

J Med Genet 2020 Jun 22. Epub 2020 Jun 22.

Neurogenetics Unit, 1st Department of Neurology, National and Kapodistrian University of Athens, Eginition University Hospital, Athens, Greece

Background: Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is an X-linked motor neuron disorder caused by an expanded CAG repeat in the gene coding for the androgen receptor (AR). The range and significance of reduced penetrance alleles in SBMA has not been fully determined to date. We presently sought to determine the range of reduced penetrance alleles in SBMA. Read More

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http://dx.doi.org/10.1136/jmedgenet-2020-106963DOI Listing

Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1 Mouse Model of Amyotrophic Lateral Sclerosis.

Nutrients 2020 Jun 18;12(6). Epub 2020 Jun 18.

Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA.

Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by motor neuron apoptosis and subsequent skeletal muscle atrophy caused by oxidative and nitrosative stress, mitochondrial dysfunction, and neuroinflammation. Anthocyanins are polyphenolic compounds found in berries that possess neuroprotective and anti-inflammatory properties. Protocatechuic acid (PCA) is a phenolic acid metabolite of the parent anthocyanin, kuromanin, found in blackberries and bilberries. Read More

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http://dx.doi.org/10.3390/nu12061824DOI Listing

Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside.

Cells 2020 Jun 18;9(6). Epub 2020 Jun 18.

Department of Neurobiology and Physiology, Xinxiang Medical University, Xinxiang 453003, Henan, China.

Parkinson's Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Read More

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http://dx.doi.org/10.3390/cells9061489DOI Listing

The Impact of Mitochondrial Dysfunction on Dopaminergic Neurons in the Olfactory Bulb and Odor Detection.

Mol Neurobiol 2020 Jun 20. Epub 2020 Jun 20.

Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, University of Cologne, Cologne, Germany.

Understanding non-motor symptoms of Parkinson's disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson's disease patients. Mitochondrial dysfunction is a key feature in Parkinson's disease and importantly contributes to the selective loss of dopaminergic neurons the substantia nigra pars compacta. Read More

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http://dx.doi.org/10.1007/s12035-020-01947-wDOI Listing

Multiple Roles of Transforming Growth Factor Beta in Amyotrophic Lateral Sclerosis.

Int J Mol Sci 2020 Jun 16;21(12). Epub 2020 Jun 16.

Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milano, Italy.

Transforming growth factor beta (TGFB) is a pleiotropic cytokine known to be dysregulated in many neurodegenerative disorders and particularly in amyotrophic lateral sclerosis (ALS). This motor neuronal disease is non-cell autonomous, as it affects not only motor neurons but also the surrounding glial cells, and the target skeletal muscle fibers. Here, we analyze the multiple roles of TGFB in these cell types, and how TGFB signaling is altered in ALS tissues. Read More

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http://dx.doi.org/10.3390/ijms21124291DOI Listing

Spreading in ALS: The relative impact of upper and lower motor neuron involvement.

Ann Clin Transl Neurol 2020 Jun 18. Epub 2020 Jun 18.

Institute of Physiology, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

Objective: To investigate disease spread in amyotrophic lateral sclerosis (ALS), and determine the influence of lower (LMN) and upper motor neuron (UMN) involvement.

Methods: We assessed disease spread in ALS in 1376 consecutively studied patients, from five European centers, applying an agreed proforma to assess LMN and UMN signs. We defined the pattern of disease onset and progression from predominant UMN or lower motor neuron (LMN) dysfunction in bulbar, upper limbs, lower limbs, and thoracic regions Non-linear regression analysis was applied to fit the data to a model that described the relation between two random variables, graphically represented by an inverse exponential curve. Read More

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http://dx.doi.org/10.1002/acn3.51098DOI Listing

MicroRNA-183-5p is stress-inducible and protects neurons against cell death in amyotrophic lateral sclerosis.

J Cell Mol Med 2020 Jun 18. Epub 2020 Jun 18.

Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons. A fundamental pathogenesis of ALS is the prolonged cell stress in neurons, which is caused by either accumulation of protein aggregates or reactive oxygen species. However, the mechanistic link between stress sensing and cell death is unsettled. Read More

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http://dx.doi.org/10.1111/jcmm.15490DOI Listing

"Switchboard" malfunction in motor neuron diseases: Selective pathology of thalamic nuclei in amyotrophic lateral sclerosis and primary lateral sclerosis.

Neuroimage Clin 2020 May 30;27:102300. Epub 2020 May 30.

Computational Neuroimaging Group, Biomedical Sciences Institute, Trinity College Dublin, Ireland. Electronic address:

The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. Read More

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http://dx.doi.org/10.1016/j.nicl.2020.102300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303672PMC

Characteristics of circular RNAs generated by human Survival Motor Neuron genes.

Cell Signal 2020 Jun 15;73:109696. Epub 2020 Jun 15.

Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States of America. Electronic address:

Circular RNAs (circRNAs) belong to a diverse class of stable RNAs expressed in all cell types. Their proposed functions include sponging of microRNAs (miRNAs), sequestration and trafficking of proteins, assembly of multimeric complexes, production of peptides, and regulation of transcription. Backsplicing due to RNA structures formed by an exceptionally high number of Alu repeats lead to the production of a vast repertoire of circRNAs by human Survival Motor Neuron genes, SMN1 and SMN2, that code for SMN, an essential multifunctional protein. Read More

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http://dx.doi.org/10.1016/j.cellsig.2020.109696DOI Listing
June 2020
4.315 Impact Factor

Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China.

BMC Med Genet 2020 Jun 18;21(1):133. Epub 2020 Jun 18.

The Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Add: No. 1, Jianshe East Rd, Erqi District, Zhengzhou, Henan Province, China.

Background: Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e. Read More

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http://dx.doi.org/10.1186/s12881-020-01069-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302341PMC

Wisdom of the expert crowd prediction of response for 3 neurology randomized trials.

Neurology 2020 Jun 16. Epub 2020 Jun 16.

From Pytho LLC (P.A.), Brooklyn, NY; Department of Neurology (A.D.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Biomedical Ethics Unit, Department of Social Studies of Medicine (A.M., E.V., D.M.B., J.K.), and Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital (I.S.), McGill University, Montreal, Canada; Max Delbrueck Center for Molecular Medicine (F.P.), Berlin; Department of Neurology (F.P.), NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin; Humboldt-Universität zu Berlin (U.D.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin; and Department of Experimental Neurology and Center for Stroke Research Berlin and QUEST Center for Transforming Biomedical Research (U.D.), Berlin Institute of Health, Germany.

Objective: To explore the accuracy of combined neurology expert forecasts in predicting primary endpoints for trials.

Methods: We identified one major randomized trial each in stroke, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) that was closing within 6 months. After recruiting a sample of neurology experts for each disease, we elicited forecasts for the primary endpoint outcomes in the trial placebo and treatment arms. Read More

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http://dx.doi.org/10.1212/WNL.0000000000009819DOI Listing

Neuropathy-associated histidyl-tRNA synthetase variants attenuate protein synthesis in vitro and disrupt axon outgrowth in developing zebrafish.

FEBS J 2020 Jun 15. Epub 2020 Jun 15.

Department of Biochemistry, University of Vermont, Burlington, United States.

Charcot-Marie-Tooth disease (CMT) encompasses a set of genetically and clinically heterogeneous neuropathies characterized by length dependent dysfunction of the peripheral nervous system. Mutations in over 80 diverse genes are associated with CMT, and aminoacyl-tRNA synthetases (ARS) constitute a large gene family implicated in the disease. Despite considerable efforts to elucidate the mechanistic link between ARS mutations and the CMT phenotype, the molecular basis of the pathology is unknown. Read More

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http://dx.doi.org/10.1111/febs.15449DOI Listing

[Effect of benzo(a)pyrene on dopaminergic neurons and α-synuclein in brain and its mechanism involved].

Beijing Da Xue Xue Bao Yi Xue Ban 2020 Jun;52(3):438-443

Department of Occupational and Environmental Health, Peking University School of Public Health, Beijing 100191, China.

Objective: To analyze the effect of benzopyrene on the decrease of dopaminergic neurons, and the increase and aggregation of α-synuclein, which are the pathological features of Parkinson's disease, and to explore its possible mechanisms.

Methods: Eight-month-old transgenic mice with human gene were randomly divided into a BaP-exposed group and a control group. BaP and solvent corn oil were injected intraperitoneally to BaP-exposed group and control group respectively, once a day for 60 days. Read More

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http://dx.doi.org/10.19723/j.issn.1671-167X.2020.03.007DOI Listing

Is cell-based therapy more efficacious for people with amyotrophic lateral sclerosis/motor neuron disease than placebo or no treatment? - A Cochrane review summary with commentary.

NeuroRehabilitation 2020 Jun 12. Epub 2020 Jun 12.

Department of Experimental and Clinical Medicine- Politecnica delle Marche University, Ancona, Italy. E-mail:

Background: Even if there is sparse evidence of efficacy of stem cell administration for amyotrophic lateral sclerosis (ALS) in preclinical studies, the clinical use of cell-based therapy is yet to be defined.

Objective: to assess the efficacy, feasibility and safety of cell-based therapy in people with ALS/MND., compared with placebo or no treatment. Read More

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http://dx.doi.org/10.3233/NRE-209004DOI Listing