24,792 results match your criteria Amyotrophic Lateral Sclerosis


Smoking and Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

Ann Neurol 2019 Feb 20. Epub 2019 Feb 20.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

In this study, we examined the potential causal effect of smoking on amyotrophic lateral sclerosis using the Project MinE data involving 12,577 patients with amyotrophic lateral sclerosis and 23,475 controls in a Mendelian randomization (MR) framework. The MR approach has the potential to investigate causal relationship between a risk factor and a disease, avoiding confounding and information bias that often present in conventional epidemiological studies. We found that smokers had a higher risk of amyotrophic lateral sclerosis compared to never smokers. Read More

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http://dx.doi.org/10.1002/ana.25443DOI Listing
February 2019

Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta-analysis and systematic review.

J Neurochem 2019 Feb 20. Epub 2019 Feb 20.

Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.

Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. Read More

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http://dx.doi.org/10.1111/jnc.14686DOI Listing
February 2019

TDP-43: A KEY THERAPEUTIC TARGET BEYOND AMYOTROPHIC LATERAL SCLEROSIS.

ACS Chem Neurosci 2019 Feb 20. Epub 2019 Feb 20.

Accumulation of TDP-43 in the cytoplasm of diseased neurons is the pathological hallmark of Frontotemporal Dementia-TDP (FTLD-TDP) and Amyotrophic Lateral Sclerosis (ALS), two diseases that lack of efficacious medicine to prevent or to stop disease progression. The discovery that mutations in the TARDBP gene (coding for the nuclear protein known as TDP-43) in both FTLD and ALS patients provided evidence for a link between TDP-43 alterations and neurodegeneration. The knowledge of TDP-43 function has advanced profoundly in the last years, however its complete role and the molecular mechanisms that lead to disease have yet to be fully understood. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00026DOI Listing
February 2019

Early post-marketing experience with edaravone in an unselected group of patients with ALS.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Feb 20:1-4. Epub 2019 Feb 20.

a Department of Neurology , Neuromuscular Diseases Unit, Tel Aviv Sourasky Medical Center , Tel Aviv , Israel.

Introduction: Treatment with edaravone has shown efficacy in a subgroup of patients with amyotrophic lateral sclerosis (ALS). However, it has been estimated that <7% of ALS patients fulfill the stringent inclusion criteria of the trial. In the current study, we aimed to explore retrospectively the efficacy of edaravone in unselected ALS patients. Read More

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https://www.tandfonline.com/doi/full/10.1080/21678421.2019.1
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http://dx.doi.org/10.1080/21678421.2019.1572191DOI Listing
February 2019
1 Read

Clinical disease stage related changes of serological factors in amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Feb 20:1-8. Epub 2019 Feb 20.

a Department of Neurology , West China Hospital, Sichuan University , Chengdu , Sichuan , China.

Objective: Little is known whether disease clinical stage would influence the serological values in Amyotrophic lateral sclerosis (ALS). We aimed to explore the association between the levels of serological factors with clinical progression determined by the King's College staging system.

Methods: ALS Patients were registered from May 2008 to December 2016. Read More

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http://dx.doi.org/10.1080/21678421.2018.1550516DOI Listing
February 2019

Therapeutic blockade of HMGB1 reduces early motor deficits, but not survival in the SOD1 mouse model of amyotrophic lateral sclerosis.

J Neuroinflammation 2019 Feb 19;16(1):45. Epub 2019 Feb 19.

Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disease without effective treatment. The receptor for advanced glycation end products (RAGE) and the toll-like receptor (TLR) system are major components of the innate immune system, which have been implicated in ALS pathology. Extracellularly released high-mobility group box 1 (HMGB1) is a pleiotropic danger-associated molecular pattern (DAMP), and is an endogenous ligand for both RAGE and TLR4. Read More

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http://dx.doi.org/10.1186/s12974-019-1435-2DOI Listing
February 2019

Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes.

Neurogenetics 2019 Feb 19. Epub 2019 Feb 19.

Department of Genetics, Institute of Psychiatry and Neurology, Sobieskiego 9 Street, 02-957, Warsaw, Poland.

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Numerous genes linked to HSPs, overlapping phenotypes between HSP subtypes and other neurodegenerative disorders and the HSPs' dual mode of inheritance (both dominant and recessive) make the genetic diagnosis of HSPs complex and difficult. Out of the original HSP cohort comprising 306 index cases (familial and isolated) who had been tested according to "traditional workflow/guidelines" by Multiplex Ligation-dependent Probe Amplification (MLPA) and Sanger sequencing, 30 unrelated patients (all familial cases) with unsolved genetic diagnoses were tested using next-generation sequencing (NGS). Read More

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http://dx.doi.org/10.1007/s10048-019-00565-6DOI Listing
February 2019

Artificial MicroRNAs Targeting C9orf72 Can Reduce Accumulation of Intra-nuclear Transcripts in ALS and FTD Patients.

Mol Ther Nucleic Acids 2019 Jan 30;14:593-608. Epub 2019 Jan 30.

Department of Research & Development, uniQure Biopharma B.V., Amsterdam, the Netherlands. Electronic address:

The most common pathogenic mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an intronic GGGGCC (GC) repeat in the chromosome 9 open reading frame 72 (C9orf72) gene. Cellular toxicity due to RNA foci and dipeptide repeat (DPR) proteins produced by the sense and antisense repeat-containing transcripts is thought to underlie the pathogenesis of both diseases. RNA sequencing (RNA-seq) data of C9orf72-ALS patients and controls were analyzed to better understand the sequence conservation of C9orf72 in patients. Read More

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http://dx.doi.org/10.1016/j.omtn.2019.01.010DOI Listing
January 2019

Contact Sports as a Risk Factor for Amyotrophic Lateral Sclerosis: A Systematic Review.

Global Spine J 2019 Feb 31;9(1):104-118. Epub 2019 Jan 31.

Swedish Neuroscience Institute, Seattle, WA, USA.

Study Design: Systematic review.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, ultimately resulting in paralysis and death. The condition is considered to be caused by a complex interaction between environmental and genetic factors. Read More

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http://dx.doi.org/10.1177/2192568218813916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362556PMC
February 2019

Molecular Mechanisms of Neurodegeneration Related to Hexanucleotide Repeat Expansion.

Behav Neurol 2019 15;2019:2909168. Epub 2019 Jan 15.

Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.

Two clinically distinct diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), have recently been classified as two extremes of the FTD/ALS spectrum. The neuropathological correlate of FTD is frontotemporal lobar degeneration (FTLD), characterized by tau-, TDP-43-, and FUS-immunoreactive neuronal inclusions. An earlier discovery that a hexanucleotide repeat expansion mutation in chromosome 9 open reading frame 72 () gene causes ALS and FTD established a special subtype of ALS and FTLD with TDP-43 pathology (C9FTD/ALS). Read More

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http://dx.doi.org/10.1155/2019/2909168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350563PMC
January 2019

A standard operating procedure for King's ALS clinical staging.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Feb 18:1-6. Epub 2019 Feb 18.

c Department of Basic and Clinical Neuroscience , Maurice Wohl Clinical Neuroscience Institute, King's College London , London , UK.

Objective: Clinical stages in amyotrophic lateral sclerosis (ALS) can be measured using a simple system based on the number of CNS regions involved and requirement for gastrostomy or noninvasive ventilation (NIV). We aimed to design a standard operating procedure (SOP) to define the standardized use and application of the King's staging system.

Methods: We designed a SOP for the King's staging system. Read More

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http://dx.doi.org/10.1080/21678421.2018.1556696DOI Listing
February 2019

Ultrasound-Guided Botulinum Toxin Injections into the Salivary Glands for the Treatment of Drooling.

Isr Med Assoc J 2019 Feb;21(2):116-119

Department of Oral and Maxillofacial Surgery, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Drooling is the unintentional loss of saliva from the mouth, usually caused by poor coordination of the swallowing mechanism. It is commonly seen in patients with chronic neurologic disorders, such as Parkinson's disease, amyotrophic lateral sclerosis (ALS), cerebral palsy, and stroke, as well as in patients with cognitive impairment and dementia.

Objectives: To evaluate the efficacy and safety of ultrasound-guided botulinum toxin injections into the parotid and submandibular salivary glands for the treatment of drooling. Read More

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February 2019
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Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030;

Genome damage and their defective repair have been etiologically linked to degenerating neurons in many subtypes of amyotrophic lateral sclerosis (ALS) patients; however, the specific mechanisms remain enigmatic. The majority of sporadic ALS patients feature abnormalities in the transactivation response DNA-binding protein of 43 kDa (TDP-43), whose nucleo-cytoplasmic mislocalization is characteristically observed in spinal motor neurons. While emerging evidence suggests involvement of other RNA/DNA binding proteins, like FUS in DNA damage response (DDR), the role of TDP-43 in DDR has not been investigated. Read More

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http://www.pnas.org/lookup/doi/10.1073/pnas.1818415116
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http://dx.doi.org/10.1073/pnas.1818415116DOI Listing
February 2019
5 Reads

The underacknowledged PPA-ALS: A unique clinicopathologic subtype with strong heritability.

Neurology 2019 Feb 15. Epub 2019 Feb 15.

From the Brain and Mind Centre and Central Clinical School (R.H.T., B.G., C.D.-S., J.B.J.K., M.C.K., J.R.H., G.M.H.) and School of Medical Sciences (J.J.K.), Faculty of Medicine and Health, and Brain and Mind Centre and School of Psychology (O.P.), The University of Sydney; School of Medical Sciences (R.H.T., C.D.-S., G.M.H.), University of New South Wales & Neuroscience Research Australia; Department of Neurology (M.C.K.), Royal Prince Alfred Hospital; ARC Centre of Excellence in Cognition and its Disorders (J.R.H., O.P.); and Division of Neuroscience (B.G.), Garvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, New South Wales, Australia.

Objective: To assess the incidence, heritability, and neuropathology of primary progressive aphasia (PPA) with amyotrophic lateral sclerosis (ALS) in a large Australian cohort.

Methods: A total of 130 patients with a primary nonfluent variant of PPA (nfvPPA) or semantic variant of PPA (svPPA) were assessed for concomitant ALS and a strong family history of neurodegenerative diseases (Goldman score ≤3). Neuropathologic examination was carried out in 28% (n = 36) of these PPA and PPA-ALS cases that had come to autopsy. Read More

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http://dx.doi.org/10.1212/WNL.0000000000007146DOI Listing
February 2019
2 Reads

Corrigendum to "Driven to decay: Excitability and synaptic abnormalities in amyotrophic lateral sclerosis" [Brain Research Bulletin 140 (2018) 318-333].

Brain Res Bull 2019 Mar;146:327

Department of Physiology and biomedical engineering,Mayo Clinic, Rochester, MN,USA; School of Biomedical sciences, The University of Queensland,St Lucia, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.brainresbull.2019.02.007DOI Listing
March 2019
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Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy.

Mol Neurodegener 2019 02 15;14(1). Epub 2019 Feb 15.

Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.

Background: A GC hexanucleotide repeat expansion in the noncoding region of C9orf72 is the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). Putative disease mechanisms underlying c9FTD/ALS include toxicity from sense GC and antisense GC repeat-containing RNA, and from dipeptide repeat (DPR) proteins unconventionally translated from these RNA products.

Methods: Intracerebroventricular injections with adeno-associated virus (AAV) encoding 2 or 149 GC repeats were performed on postnatal day 0, followed by assessment of behavioral and neuropathological phenotypes. Read More

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http://dx.doi.org/10.1186/s13024-019-0310-zDOI Listing
February 2019
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C9orf72-dependent lysosomal functions regulate epigenetic control of autophagy and lipid metabolism.

Authors:
Yang Liu Jiou Wang

Autophagy 2019 Feb 15:1-2. Epub 2019 Feb 15.

a Department of Biochemistry and Molecular Biology, Department of Neuroscience , Johns Hopkins University , Baltimore , MD , USA.

Cellular adaption to nutrient stress is exquisitely regulated, and its dysregulation could underlie human diseases including neurodegeneration. C9orf72 is linked to the most common forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as well as rare cases of other neurological disorders. Recent studies have implicated C9orf72 functions in the autophagy-lysosome pathway, but the exact roles of C9orf72 remain unclear. Read More

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http://dx.doi.org/10.1080/15548627.2019.1580106DOI Listing
February 2019
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Heterochromatin anomalies and double-stranded RNA accumulation underlie poly(PR) toxicity.

Science 2019 02;363(6428)

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

How hexanucleotide GGGGCC (GC) repeat expansions in cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is not understood. We developed a mouse model engineered to express poly(PR), a proline-arginine (PR) dipeptide repeat protein synthesized from expanded GC repeats. The expression of green fluorescent protein-conjugated (PR) (a 50-repeat PR protein) throughout the mouse brain yielded progressive brain atrophy, neuron loss, loss of poly(PR)-positive cells, and gliosis, culminating in motor and memory impairments. Read More

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http://dx.doi.org/10.1126/science.aav2606DOI Listing
February 2019
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Implications of Microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

J Mol Biol 2019 Feb 11. Epub 2019 Feb 11.

Group of Stem Cells and Modeling of Neurodegeneration, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, Grønnegårdsvej 7, 1870C. Electronic address:

Amyotrophic lateral sclerosis (ALS) and Frontotemporal dementia (FTD) are neurodegenerative disorders with clear similarities regarding their clinical, genetic and pathological features. Both are progressive, lethal disorders, with no current curative treatment available. Several genes correlated with ALS and FTD are implicated in the same molecular pathways. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00222836193006
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http://dx.doi.org/10.1016/j.jmb.2019.02.004DOI Listing
February 2019
6 Reads

Muscle secretion of toxic factors, regulated by miR126-5p, facilitates motor neuron degeneration in amyotrophic lateral sclerosis.

Neural Regen Res 2019 Jun;14(6):969-970

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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http://dx.doi.org/10.4103/1673-5374.250571DOI Listing
June 2019
1 Read

Lessons from glaucoma: rethinking the fluid-brain barriers in common neurodegenerative disorders.

Neural Regen Res 2019 Jun;14(6):962-966

Department of Surgery, Faculty of Medicine, University of Granada, Granada, Spain.

Glaucoma has been recently characterized as a member of the group of anoikis-related diseases. Anoikis, a form of apoptosis, can be triggered by the unfastening of adherent junctions present in astrocytes. In those areas of the central nervous system in which the soma of the neurons or their axons and dendrites are metabolically dependent on the activity of astrocytes, a derangement of the lactate shuttle caused by a separation between the plasma membranes of neurons and astrocytes would result in metabolic impairment of the neurons themselves. Read More

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http://www.nrronline.org/text.asp?2019/14/6/962/249215
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http://dx.doi.org/10.4103/1673-5374.249215DOI Listing
June 2019
4 Reads

Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases.

Neural Regen Res 2019 Jun;14(6):931-938

Department of Hand Surgery, the Second Hospital of Jilin University, Changchun, Jilin Province, China.

Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. Read More

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http://www.nrronline.org/text.asp?2019/14/6/931/250570
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http://dx.doi.org/10.4103/1673-5374.250570DOI Listing
June 2019
6 Reads

High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis.

J Neurol Neurosurg Psychiatry 2019 Feb 13. Epub 2019 Feb 13.

Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.

Objective: To determine whether persistent organic pollutants (POP) affect amyotrophic lateral sclerosis (ALS) survival.

Methods: ALS participants seen at the University of Michigan (Ann Arbor, MI, USA) provided plasma samples for measurement of POPs. ALS disease and clinical features were collected prospectively from the medical records. Read More

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http://jnnp.bmj.com/lookup/doi/10.1136/jnnp-2018-319785
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http://dx.doi.org/10.1136/jnnp-2018-319785DOI Listing
February 2019
2 Reads

Measuring network disruption in neurodegenerative diseases: New approaches using signal analysis.

J Neurol Neurosurg Psychiatry 2019 Feb 13. Epub 2019 Feb 13.

Academic Unit of Neurology, Trinity College Dublin, the University of Dublin, Dublin, Ireland

Advanced neuroimaging has increased understanding of the pathogenesis and spread of disease, and offered new therapeutic targets. MRI and positron emission tomography have shown that neurodegenerative diseases including Alzheimer's disease (AD), Lewy body dementia (LBD), Parkinson's disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are associated with changes in brain networks. However, the underlying neurophysiological pathways driving pathological processes are poorly defined. Read More

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http://jnnp.bmj.com/lookup/doi/10.1136/jnnp-2018-319581
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http://dx.doi.org/10.1136/jnnp-2018-319581DOI Listing
February 2019
2 Reads

Charity financial support to motor neuron disease (MND) patients in Greater London: the impact of patients' socioeconomic status-a cross-sectional study.

BMJ Open 2019 Feb 12;9(2):e022462. Epub 2019 Feb 12.

Centre for Primary Care and Public Health, Queen Mary University of London, London, UK.

Objective: There is an immense socioeconomic burden for both the patients with motor neuron disease (MND) and their families. The aim of this study is to evaluate the extent to which the provision offered by the Motor Neurone Disease Association is distributed among patients with MND living in the ethnically and socially diverse area of Greater London, according to the patients' socioeconomic situation and needs.

Setting: Greater London, where age and sex-adjusted prevalence rates of MND in 2016 were calculated. Read More

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http://dx.doi.org/10.1136/bmjopen-2018-022462DOI Listing
February 2019
1 Read

TDP-43 regulates site-specific 2'-O-methylation of U1 and U2 snRNAs via controlling the Cajal body localization of a subset of C/D scaRNAs.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Department of Applied Biological Science and Global Innovation Research Organizations, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.

TDP-43 regulates cellular levels of Cajal bodies (CBs) that provide platforms for the assembly and RNA modifications of small nuclear ribonucleoproteins (snRNPs) involved in pre-mRNA splicing. Alterations in these snRNPs may be linked to pathogenesis of amyotrophic lateral sclerosis. However, specific roles for TDP-43 in CBs remain unknown. Read More

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http://dx.doi.org/10.1093/nar/gkz086DOI Listing
February 2019
2 Reads

Modulating P1 Adenosine Receptors in Disease Progression of SOD1 Mutant Mice.

Neurochem Res 2019 Feb 12. Epub 2019 Feb 12.

National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.

Amyotrophic lateral sclerosis (ALS) is a fatal progressing neurodegenerative disease; to date, despite the intense research effort, only two therapeutic options, with very limited effects, are available. The purinergic system has been indicated as a possible new therapeutic target for ALS, but the results are often contradictory and generally confused. The present study was designed to determine whether P1 adenosine receptor ligands affected disease progression in a transgenic model of ALS. Read More

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http://dx.doi.org/10.1007/s11064-019-02745-0DOI Listing
February 2019
2 Reads

Response to Letter to the Editor: "Amyotrophic lateral sclerosis and exposure to diesel exhaust in a Danish cohort".

Am J Epidemiol 2019 Feb 11. Epub 2019 Feb 11.

Departments of Epidemiology and Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

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http://dx.doi.org/10.1093/aje/kwz023DOI Listing
February 2019
1 Read
5.230 Impact Factor

Application of quercetin in neurological disorders: from nutrition to nanomedicine.

Rev Neurosci 2019 Feb 12. Epub 2019 Feb 12.

Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan 8174673441, Iran.

Quercetin is a polyphenolic flavonoid, which is frequently found in fruits and vegetables. The antioxidant potential of quercetin has been studied from subcellular compartments, that is, mitochondria to tissue levels in the brain. The neurodegeneration process initiates alongside aging of the neurons. Read More

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http://www.degruyter.com/view/j/revneuro.ahead-of-print/revn
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http://dx.doi.org/10.1515/revneuro-2018-0080DOI Listing
February 2019
7 Reads

Overriding FUS autoregulation in mice triggers gain-of-toxic dysfunctions in RNA metabolism and autophagy-lysosome axis.

Elife 2019 Feb 12;8. Epub 2019 Feb 12.

Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, United States.

Mutations in coding and non-coding regions of FUS cause amyotrophic lateral sclerosis (ALS). The latter mutations may exert toxicity by increasing FUS accumulation. We show here that broad expression within the nervous system of wild-type or either of two ALS-linked mutants of human FUS in mice produces progressive motor phenotypes accompanied by characteristic ALS-like pathology. Read More

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http://dx.doi.org/10.7554/eLife.40811DOI Listing
February 2019
1 Read

Nuclear RNA foci from expansion mutation form paraspeckle-like bodies.

J Cell Sci 2019 02 11. Epub 2019 Feb 11.

Department of Biotechnology, Jozef Stefan Institute, Ljubljana 1000, Slovenia

The GGGGCC (GC) repeat expansion mutation in gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Transcription of the repeat and formation of nuclear RNA foci, which sequester specific RNA-binding proteins is one of the possible pathological mechanisms. Here, we show that (GC) repeat RNA predominantly associates with essential paraspeckle proteins SFPQ, NONO, RBM14, FUS and hnRNPH and co-localizes with known paraspeckle-associated RNA As formation of paraspeckles in motor neurons has been associated with early phases of ALS, we investigated the extent of similarity between paraspeckles and (GC) RNA foci. Read More

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http://jcs.biologists.org/lookup/doi/10.1242/jcs.224303
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http://dx.doi.org/10.1242/jcs.224303DOI Listing
February 2019
3 Reads

Aerobic Exercise Therapy in Ambulatory Patients With ALS: A Randomized Controlled Trial.

Neurorehabil Neural Repair 2019 Feb;33(2):153-164

1 University Medical Center Utrecht, Netherlands.

Background: Weakness caused by motor neuron degeneration in amyotrophic lateral sclerosis (ALS) may result in avoidance of physical activity, resulting in deconditioning and reduced health-related quality of life (HRQoL).

Objective: To study the effectiveness of aerobic exercise therapy (AET) on disease-specific and generic HRQoL in ambulatory patients with ALS.

Methods: We conducted a multicenter, assessor-blinded, randomized controlled trial. Read More

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http://journals.sagepub.com/doi/10.1177/1545968319826051
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http://dx.doi.org/10.1177/1545968319826051DOI Listing
February 2019
2 Reads

RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43.

J Mol Biol 2019 Feb 8. Epub 2019 Feb 8.

UK Dementia Research Institute at King's College London, London, SE5 9RT, United Kingdom; The Wohl Institute at King's College London, London, SE5 9RT, United Kingdom; Department of Medicina Molecolare, University of Pavia, Pavia, 27100, Italy. Electronic address:

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTD) are incurable motor neuron diseases associated with muscle weakness, paralysis and respiratory failure. Accumulation of TAR DNA-binding protein 43 (TDP-43) as toxic cytoplasmic inclusions is one of the hallmarks of these pathologies. TDP-43 is an RNA-binding protein responsible for regulating RNA transcription, splicing, transport and translation. Read More

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http://dx.doi.org/10.1016/j.jmb.2019.01.028DOI Listing
February 2019
2 Reads

TDP-43 proteinopathy in Theiler's murine encephalomyelitis virus infection.

PLoS Pathog 2019 Feb 11;15(2):e1007574. Epub 2019 Feb 11.

Departments of Neurology, University of Chicago Medical Center, Chicago, IL, United States of America.

TDP-43, an RNA-binding protein that is primarily nuclear and important in splicing and RNA metabolism, is mislocalized from the nucleus to the cytoplasm of neural cells in amyotrophic lateral sclerosis (ALS), and contributes to disease. We sought to investigate whether TDP-43 is mislocalized in infections with the acute neuronal GDVII strain and the persistent demyelinating DA strain of Theiler's virus murine encephalomyelitis virus (TMEV), a member of the Cardiovirus genus of Picornaviridae because: i) L protein of both strains is known to disrupt nucleocytoplasmic transport, including transport of polypyrimidine tract binding protein, an RNA-binding protein, ii) motor neurons and oligodendrocytes are targeted in both TMEV infection and ALS. TDP-43 phosphorylation, cleavage, and cytoplasmic mislocalization to an aggresome were observed in wild type TMEV-infected cultured cells, with predicted splicing abnormalities. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007574DOI Listing
February 2019
2 Reads

Protein misfolding and aggregation in neurodegenerative diseases: a review of pathogeneses, novel detection strategies, and potential therapeutics.

Rev Neurosci 2019 Feb 12. Epub 2019 Feb 12.

Department of Physiology and Biophysics, Stony Brook University School of Medicine, 101 Nicolls Road, Health Sciences Center, Stony Brook, NY 11794-8434, USA.

Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include transcription, translation, post-translational modifications, degradation through the ubiquitin-proteasome system, and autophagy. Read More

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http://dx.doi.org/10.1515/revneuro-2016-0035DOI Listing
February 2019
2 Reads

The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration.

Authors:
Paulo A Ferreira

Cell Mol Life Sci 2019 Feb 11. Epub 2019 Feb 11.

Duke University Medical Center, DUEC 3802, 2351 Erwin Road, Durham, NC, 27710, USA.

The nuclear pore is the gatekeeper of nucleocytoplasmic transport and signaling through which a vast flux of information is continuously exchanged between the nuclear and cytoplasmic compartments to maintain cellular homeostasis. A unifying and organizing principle has recently emerged that cements the notion that several forms of amyotrophic lateral sclerosis (ALS), and growing number of other neurodegenerative diseases, co-opt the dysregulation of nucleocytoplasmic transport and that this impairment is a pathogenic driver of neurodegeneration. The understanding of shared pathomechanisms that underpin neurodegenerative diseases with impairments in nucleocytoplasmic transport and how these interface with current concepts of nucleocytoplasmic transport is bound to illuminate this fundamental biological process in a yet more physiological context. Read More

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http://dx.doi.org/10.1007/s00018-019-03029-0DOI Listing
February 2019
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Tau and TDP-43 proteinopathies: kindred pathologic cascades and genetic pleiotropy.

Lab Invest 2019 Feb 11. Epub 2019 Feb 11.

University of Kentucky College of Medicine, Lexington, KY, USA.

We review the literature on Tau and TDP-43 proteinopathies in aged human brains and the relevant underlying pathogenetic cascades. Complex interacting pathways are implicated in Alzheimer's disease and related dementias (ADRD), wherein multiple proteins tend to misfold in a manner that is "reactive," but, subsequently, each proteinopathy may contribute strongly to the clinical symptoms. Tau proteinopathy exists in brains of individuals across a broad spectrum of primary underlying conditions-e. Read More

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http://dx.doi.org/10.1038/s41374-019-0196-yDOI Listing
February 2019
2 Reads

Association between TDP-43 and mitochondria in inclusion body myositis.

Lab Invest 2019 Feb 11. Epub 2019 Feb 11.

Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

Inclusion body myositis (IBM) is the most common cause of primary myopathy in individuals aged 50 years and over, and is pathologically characterized by protein aggregates of p62 and mislocalized cytoplasmic TDP-43, as well as mitochondrial abnormalities in affected muscle fibers. Our recent studies have shown the accumulation of TDP-43 in mitochondria in neurons from patients with amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), and revealed mitochondria as critical mediators of TDP-43 neurotoxicity. In this study, we investigated the association between mitochondria and TDP-43 in biopsied skeletal muscle samples from IBM patients. Read More

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http://dx.doi.org/10.1038/s41374-019-0233-xDOI Listing
February 2019
2 Reads

VAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway.

Autophagy 2019 Feb 11:1-20. Epub 2019 Feb 11.

a Program in Developmental Biology , Baylor College of Medicine , Houston , TX , USA.

Mutations in the ER-associated VAPB/ALS8 protein cause amyotrophic lateral sclerosis and spinal muscular atrophy. Previous studies have argued that ER stress may underlie the demise of neurons. We find that loss of VAP proteins (VAPs) leads to an accumulation of aberrant lysosomes and impairs lysosomal degradation. Read More

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http://dx.doi.org/10.1080/15548627.2019.1580103DOI Listing
February 2019
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Rab-dependent cellular trafficking and amyotrophic lateral sclerosis.

Crit Rev Biochem Mol Biol 2018 Dec;53(6):623-651

a Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, Centre for MND Research , Macquarie University , Sydney , Australia.

Rab GTPases are becoming increasingly implicated in neurodegenerative disorders, although their role in amyotrophic lateral sclerosis (ALS) has been somewhat overlooked. However, dysfunction of intracellular transport is gaining increasing attention as a pathogenic mechanism in ALS. Many previous studies have focused axonal trafficking, and the extreme length of axons in motor neurons may contribute to their unique susceptibility in this disorder. Read More

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https://www.tandfonline.com/doi/full/10.1080/10409238.2018.1
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http://dx.doi.org/10.1080/10409238.2018.1553926DOI Listing
December 2018
6 Reads

Reaction to Endoplasmic Reticulum Stress ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging.

Front Aging Neurosci 2019 25;11. Epub 2019 Jan 25.

Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.

Amyotrophic lateral sclerosis (ALS) is a multisystemic neurodegenerative disorder. Given that peripheral blood mononuclear cells (PBMCs) serve as a "window to the central nervous system" we aimed to answer whether endoplasmic reticulum (ER) stress in ALS-PBMCs is related to disease aggressiveness. We studied ER stress in the PBMCs of 49 patients with ALS and 31 age- and sex-matched healthy controls. Read More

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https://www.frontiersin.org/article/10.3389/fnagi.2019.00005
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http://dx.doi.org/10.3389/fnagi.2019.00005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355670PMC
January 2019
4 Reads

Dysfunction of attention switching networks in amyotrophic lateral sclerosis.

Neuroimage Clin 2019 Feb 2;22:101707. Epub 2019 Feb 2.

Academic Unit of Neurology, Trinity College Dublin, The University of Dublin, Ireland. Electronic address:

Objective: To localise and characterise changes in cognitive networks in Amyotrophic Lateral Sclerosis (ALS) using source analysis of mismatch negativity (MMN) waveforms.

Rationale: The MMN waveform has an increased average delay in ALS. MMN has been attributed to change detection and involuntary attention switching. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22131582193005
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http://dx.doi.org/10.1016/j.nicl.2019.101707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365983PMC
February 2019
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Bone-marrow mononuclear cell therapy in a mouse model of amyotrophic lateral sclerosis: Functional outcomes from different administration routes.

Brain Res 2019 Feb 5. Epub 2019 Feb 5.

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a chronic degenerative disease that mainly affects motor neurons, leading to progressive paralysis and death. Recently, cell therapy has emerged as a therapeutic alternative for several neurological diseases, including ALS, and bone-marrow cells are one of the major cell sources. Considering the importance of pre-clinical trials to determine the best therapeutic protocol and the hope of translating this protocol to the clinical setting, we tested bone-marrow mononuclear cell (BMMC) therapy administered by different routes in the SOD1 model of ALS. Read More

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http://dx.doi.org/10.1016/j.brainres.2019.02.003DOI Listing
February 2019
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Epigenetic and Neurological Impairments Associated with Early Life Exposure to Persistent Organic Pollutants.

Int J Genomics 2019 14;2019:2085496. Epub 2019 Jan 14.

Immune Endocrine Epigenetics Research Group, Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, L-4354 Esch-sur-Alzette, Luxembourg.

The incidence of neurodevelopmental and neurodegenerative diseases worldwide has dramatically increased over the last decades. Although the aetiology remains uncertain, evidence is now growing that exposure to persistent organic pollutants during sensitive neurodevelopmental periods such as early life may be a strong risk factor, predisposing the individual to disease development later in life. Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders including neuropathies, cognitive, motor, and sensory impairments; neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD); and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Read More

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http://dx.doi.org/10.1155/2019/2085496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348822PMC
January 2019
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Enabling precision medicine by unravelling disease pathophysiology: quantifying signal transduction pathway activity across cell and tissue types.

Sci Rep 2019 Feb 7;9(1):1603. Epub 2019 Feb 7.

Philips Research, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.

Signal transduction pathways are important in physiology and pathophysiology. Targeted drugs aim at modifying pathogenic pathway activity, e.g. Read More

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http://dx.doi.org/10.1038/s41598-018-38179-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367506PMC
February 2019
2 Reads

Validation of the revised classification of cognitive and behavioural impairment in ALS.

J Neurol Neurosurg Psychiatry 2019 Feb 7. Epub 2019 Feb 7.

ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Italy

Objective: In 2017, the diagnostic criteria for cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (ALSFTD-1) have been modified (ALSFTD-2) with the inclusion of a novel category (ALS with combined cognitive and behavioural impairment, ALScbi) and with changes of operational criteria of the other categories (ALS with cognitive impairment (ALSci), ALS with behavioural impairment (ALSbi) and ALS with frontotemporal dementia (ALS-FTD)). We compared the two sets of criteria to assess the effect of the revised criteria on the cognitive classification of patients with ALS.

Methods: Two cohorts of patients with ALS were included in this study: a population-based cohort including patients identified through the Piemonte/Valle d'Aosta register for ALS in the 2014-2017 period (n=321), and a referral cohort recruited at the Turin ALS centre and at the ALS centre of the Maugeri Institute in Milan in the same period (n=205). Read More

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http://dx.doi.org/10.1136/jnnp-2018-319696DOI Listing
February 2019
2 Reads

Pseudobulbar Affect in Parkinsonian Disorders: A Review.

J Mov Disord 2019 Jan 30;12(1):14-21. Epub 2019 Jan 30.

Stony Brook University School of Medicine, Stony Brook, NY.

Pseudobulbar affect (PBA) is a neurological symptom of inappropriate and uncontrollable laughter or crying that occurs secondary to a variety of neurological conditions, including parkinsonian disorders. PBA is a socially and emotionally debilitating symptom that has been estimated to affect 3.6% to 42. Read More

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http://dx.doi.org/10.14802/jmd.18051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369372PMC
January 2019
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[Psychosocial Care For Patients With Amyotrophic Lateral Sclerosis: A Narrative Review].

Psychother Psychosom Med Psychol 2019 Feb 7. Epub 2019 Feb 7.

Abteilung für Medizinische Psychologie und Medizinische Soziologie, Universitätsklinikum Leipzig.

This narrative review gives a broad summary of the psychosocial strain in patients with amyotrophic lateral sclerosis (ALS) and psychotherapeutic interventions addressing these issues. ALS is a fatal, rapidly progressing neurodegenerative disease, which leads to weakness and atrophy in almost all muscles of the body, resulting in impairment and finally inability in all domains of daily life including mobility, food intake, respiration or communication. In addition to these mainly motor impairments, most patients are also affected by severe cognitive-emotional and behavioral alterations and deficits which may lead to additional distress. Read More

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http://dx.doi.org/10.1055/a-0806-7862DOI Listing
February 2019
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Interplay between spinal cord and cerebral cortex metabolism in amyotrophic lateral sclerosis.

Brain 2018 Aug;141(8):2272-2279

Nuclear Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, 16132, Italy.

We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Read More

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http://dx.doi.org/10.1093/brain/awy152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061793PMC
August 2018
2 Reads

An appraisal of folates as key factors in cognition and ageing-related diseases.

Crit Rev Food Sci Nutr 2019 Feb 7:1-18. Epub 2019 Feb 7.

a Radiobiology Unit , Belgian Nuclear Research Centre SCK•CEN , Mol , Belgium.

Folic acid (FA) is often consumed as a food supplement and can be found in fortified staple foods in various western countries. Even though FA supplementation during pregnancy is known to prevent severe congenital anomalies in the developing child (e.g. Read More

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https://www.tandfonline.com/doi/full/10.1080/10408398.2018.1
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http://dx.doi.org/10.1080/10408398.2018.1549017DOI Listing
February 2019
3 Reads