30,925 results match your criteria Primary Lateral Sclerosis


FTO controls reversible mAm RNA methylation during snRNA biogenesis.

Nat Chem Biol 2019 Feb 18. Epub 2019 Feb 18.

Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA.

Small nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA splicing. Here we show that snRNAs contain a regulated and reversible nucleotide modification causing them to exist as two different methyl isoforms, m and m, reflecting the methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA biogenesis involves the formation of an initial m isoform with a single-methylated adenosine (2'-O-methyladenosine, Am), which is then converted to a dimethylated m isoform (N,2'-O-dimethyladenosine, mAm). Read More

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http://dx.doi.org/10.1038/s41589-019-0231-8DOI Listing
February 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

Survey of the Ciliary Motility Machinery of Sperm and Ciliated Mechanosensory Neurons Reveals Unexpected Cell-Type Specific Variations: A Model for Motile Ciliopathies.

Front Genet 2019 1;10:24. Epub 2019 Feb 1.

Centre for Discovery Brain Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom.

The motile cilium/flagellum is an ancient eukaryotic organelle. The molecular machinery of ciliary motility comprises a variety of cilium-specific dynein motor complexes along with other complexes that regulate their activity. Assembling the motors requires the function of dedicated "assembly factors" and transport processes. Read More

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http://dx.doi.org/10.3389/fgene.2019.00024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367277PMC
February 2019

TARDBP mutation associated with semantic variant primary progressive aphasia, case report and review of the literature.

Neurocase 2019 Feb 16:1-5. Epub 2019 Feb 16.

a Department of Neurology , Hospital Universitario 12 de Octubre , Madrid , Spain.

Semantic variant primary progressive aphasia (svPPA) is a clinical syndrome included in the frontotemporal dementia (FTD) spectrum. Unlike other forms of FTD, it is sporadic in the majority of cases and not commonly associated with motor neuron disease (MND). We describe a case of svPPA associated with MND in the same family, due to a mutation of the transactive response DNA binding protein (TARDBP) gene, and review the literature. Read More

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http://dx.doi.org/10.1080/13554794.2019.1581225DOI Listing
February 2019

Dual Inhibition of GSK3β and CDK5 Protects the Cytoskeleton of Neurons from Neuroinflammatory-Mediated Degeneration In Vitro and In Vivo.

Stem Cell Reports 2019 Jan 31. Epub 2019 Jan 31.

Technische Universität Dresden, DFG-Research Center for Regenerative Therapies Dresden (CRTD), Fetscherstrasse 105, 01307 Dresden, Germany; Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany. Electronic address:

Neuroinflammation is a hallmark of neurological disorders and is accompanied by the production of neurotoxic agents such as nitric oxide. We used stem cell-based phenotypic screening and identified small molecules that directly protected neurons from neuroinflammation-induced degeneration. We demonstrate that inhibition of CDK5 is involved in, but not sufficient for, neuroprotection. Read More

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http://dx.doi.org/10.1016/j.stemcr.2019.01.015DOI Listing
January 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

Parkinson's disease and pain: Modulation of nociceptive circuitry in a rat model of nigrostriatal lesion.

Exp Neurol 2019 Feb 14;315:72-81. Epub 2019 Feb 14.

Laboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo, SP, Brazil. Electronic address:

Parkinson's disease (PD) is a neurodegenerative disorder that causes progressive dysfunction of dopaminergic and non-dopaminergic neurons, generating motor and nonmotor signs and symptoms. Pain is reported as the most bothersome nonmotor symptom in PD; however, pain remains overlooked and poorly understood. In this study, we evaluated the nociceptive behavior and the descending analgesia circuitry in a rat model of PD. Read More

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http://dx.doi.org/10.1016/j.expneurol.2019.02.007DOI Listing
February 2019

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
3 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
1 Read

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

Macroglossia, Motor Neuron Pathology, and Airway Malacia Contribute to Respiratory Insufficiency in Pompe Disease: A Commentary on Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases.

Int J Mol Sci 2019 Feb 11;20(3). Epub 2019 Feb 11.

Division of Pulmonary Medicine, Department of Pediatric, Duke University School of Medicine, Durham, NC 27710, USA.

The authors of the recently published, "Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases", provide an important review of the various mechanisms of lysosomal storage diseases (LSD) and how they culminate in similar clinical pathologies [... Read More

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http://dx.doi.org/10.3390/ijms20030751DOI Listing
February 2019
1 Read

High diagnostic yield and novel variants in very late-onset spasticity.

J Neurogenet 2019 Feb 12:1-6. Epub 2019 Feb 12.

b Hotchkiss Brain Institute, University of Calgary , Calgary , Canada.

Hereditary spastic paraplegias (HSPs) are a diverse group of genetic conditions with variable severity and onset age. From a neurogenetic clinic, we identified 14 patients with very late-onset HSP, with symptoms starting after the age of 35. In this cohort, sequencing of known genetic causes was performed using clinically available HSP sequencing panels. Read More

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http://dx.doi.org/10.1080/01677063.2019.1566326DOI Listing
February 2019
1 Read

Attenuation of ALS progression during pregnancy-lessons to be learned or just a coincidence?

Neurol Sci 2019 Feb 11. Epub 2019 Feb 11.

Department of Neurology, Clinical Hospital Centre Zagreb, Kispaticeva 12, 10000, Zagreb, Croatia.

ALS is the most frequent motor neuron disorder in adults with suggested complex relationship regarding gender. Studies investigating ALS and hormones have provided varying results. ALS onset during pregnancy is uncommon and pregnancy after the ALS symptom onset is even rarer. Read More

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http://dx.doi.org/10.1007/s10072-019-03748-zDOI Listing
February 2019

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

Dealing With Death Taboo: Discussion of Do-Not-Resuscitate Directives With Chinese Patients With Noncancer Life-Limiting Illnesses.

Am J Hosp Palliat Care 2019 Feb 11:1049909119828116. Epub 2019 Feb 11.

2 Palliative Home Care Nursing Team, Tuen Mun Hospital, NT, Hong Kong.

Background:: Noncancer patients with life-limiting diseases often receive more intensive level of care in their final days of life, with more cardiopulmonary resuscitation performed and less do-not-resuscitate (DNR) orders in place. Nevertheless, death is still often a taboo across Chinese culture, and ethnic disparities could negatively affect DNR directives completion rates.

Objectives:: We aim to explore whether Chinese noncancer patients are willing to sign their own DNR directives in a palliative specialist clinic, under a multidisciplinary team approach. Read More

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http://dx.doi.org/10.1177/1049909119828116DOI Listing
February 2019
2 Reads
1.347 Impact Factor

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

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

The Amphetamine Induced Rotation Test: A Re-Assessment of Its Use as a Tool to Monitor Motor Impairment and Functional Recovery in Rodent Models of Parkinson's Disease.

J Parkinsons Dis 2019 ;9(1):17-29

Department of Biosciences, Cardiff University, UK.

Rats and mice with unilateral damage to the nigrostriatal dopamine system-induced by neurotoxins, such as 6-hydroxydopamine, overexpression of α-synuclein, or injections of toxic synuclein protofibrils-are widely used as experimental models to mimic the loss of dopamine neurons seen in Parkinson's disease. The amphetamine rotation test is commonly used to monitor the extent of motor impairment induced by the lesion, and this test has also become the standard tool to demonstrate transplant-induced functional recovery or the efficacy of neuroprotective interventions aimed to preserve or restore DA neuron function. Although the amphetamine-induced rotation test is highly useful for this purpose it has some important pitfalls and the interpretation of the data may not always be straightforward. Read More

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http://dx.doi.org/10.3233/JPD-181525DOI Listing
January 2019

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
4 Reads

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
2 Reads

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

Intraperitoneal delivery of a novel drug-like compound improves disease severity in severe and intermediate mouse models of Spinal Muscular Atrophy.

Sci Rep 2019 Feb 7;9(1):1633. Epub 2019 Feb 7.

Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder that causes progressive muscle weakness and is the leading genetic cause of infant mortality worldwide. SMA is caused by the loss of survival motor neuron 1 (SMN1). In humans, a nearly identical copy gene is present, called SMN2. Read More

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http://dx.doi.org/10.1038/s41598-018-38208-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367425PMC
February 2019

Development of a Prognostic Model of Respiratory Insufficiency or Death in Amyotrophic Lateral Sclerosis.

Eur Respir J 2019 Feb 6. Epub 2019 Feb 6.

Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

A clinically useful model to prognose onset of respiratory insufficiency in amyotrophic lateral sclerosis (ALS) would inform disease interventions, communication, and clinical trial design. We aimed to derive and validate a clinical prognostic model for respiratory insufficiency within six months of presentation to an outpatient ALS clinic.We used multivariable logistic regression and internal cross-validation to derive a clinical prognostic model using a single-center cohort of 765 ALS patients who presented between 2006 and 2015. Read More

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http://erj.ersjournals.com/lookup/doi/10.1183/13993003.02237
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http://dx.doi.org/10.1183/13993003.02237-2018DOI Listing
February 2019
2 Reads

RNA Dysregulation in Amyotrophic Lateral Sclerosis.

Front Genet 2018 22;9:712. Epub 2019 Jan 22.

INRS-Institut Armand-Frappier, National Institute of Scientific Research, Laval, QC, Canada.

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease and is characterized by the degeneration of upper and lower motor neurons. It has become increasingly clear that RNA dysregulation is a key contributor to ALS pathogenesis. The major ALS genes , and are involved in aspects of RNA metabolism processes such as mRNA transcription, alternative splicing, RNA transport, mRNA stabilization, and miRNA biogenesis. Read More

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http://dx.doi.org/10.3389/fgene.2018.00712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349704PMC
January 2019
10 Reads

Long non-coding RNA repertoire and open chromatin regions constitute midbrain dopaminergic neuron - specific molecular signatures.

Sci Rep 2019 Feb 5;9(1):1409. Epub 2019 Feb 5.

Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.

Midbrain dopaminergic (DA) neurons are involved in diverse neurological functions, including control of movements, emotions or reward. In turn, their dysfunctions cause severe clinical manifestations in humans, such as the appearance of motor and cognitive symptoms in Parkinson's Disease. The physiology and pathophysiology of these neurons are widely studied, mostly with respect to molecular mechanisms implicating protein-coding genes. Read More

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http://dx.doi.org/10.1038/s41598-018-37872-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363776PMC
February 2019

Disrupted neuronal trafficking in amyotrophic lateral sclerosis.

Acta Neuropathol 2019 Feb 5. Epub 2019 Feb 5.

Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.

Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disease caused by degeneration of motor neurons in the brain and spinal cord leading to muscle weakness. Median survival after symptom onset in patients is 3-5 years and no effective therapies are available to treat or cure ALS. Therefore, further insight is needed into the molecular and cellular mechanisms that cause motor neuron degeneration and ALS. Read More

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http://link.springer.com/10.1007/s00401-019-01964-7
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http://dx.doi.org/10.1007/s00401-019-01964-7DOI Listing
February 2019
3 Reads

Brain Derived Neurotrophic Factor (BDNF) Delays Onset of Pathogenesis in Transgenic Mouse Model of Spinocerebellar Ataxia Type 1 (SCA1).

Front Cell Neurosci 2018 21;12:509. Epub 2019 Jan 21.

Department of Neuroscience, University of Minnesota, Minneapolis, MN, United States.

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an abnormal expansion of CAG repeats in the gene and characterized by motor deficits and cerebellar neurodegeneration. Even though mutant ATXN1 is expressed from an early age, disease onset usually occurs in patient's mid-thirties, indicating the presence of compensatory factors that limit the toxic effects of mutant ATXN1 early in disease. Brain derived neurotrophic factor (BDNF) is a growth factor known to be important for the survival and function of cerebellar neurons. Read More

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http://dx.doi.org/10.3389/fncel.2018.00509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348256PMC
January 2019

MicroRNA-26a/Death-Associated Protein Kinase 1 Signaling Induces Synucleinopathy and Dopaminergic Neuron Degeneration in Parkinson's Disease.

Biol Psychiatry 2018 Dec 19. Epub 2018 Dec 19.

Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China; National Research Center for Geriatric Diseases, Xiangya Hospital, and Center for Medical Genetics, School of Life Science, Central South University, Changsha, Hunan, China. Electronic address:

Background: Death-associated protein kinase 1 (DAPK1) is a widely distributed serine/threonine kinase that is critical for cell death in multiple neurological disorders, including Alzheimer's disease and stroke. However, little is known about the role of DAPK1 in the pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder.

Methods: We used Western blot and immunohistochemistry to evaluate the alteration of DAPK1. Read More

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http://dx.doi.org/10.1016/j.biopsych.2018.12.008DOI Listing
December 2018
3 Reads

Effects of agomelatine in rotenone-induced Parkinson's disease in rats.

Neurosci Lett 2019 Feb 1;699:71-76. Epub 2019 Feb 1.

Ondokuz Mayıs University, Medical Faculty, Department of Pharmacology, Turkey. Electronic address:

The effects of melatonin and melatonin analogs in experimental Parkinson's disease (PD) models remain controversial. Agomelatine, a novel analog of melatonin, is both agonists for melatonin-1 and melatonin-2 receptors and antagonist of 5-HTC receptors. While agomelatine has been commonly used as an anti-depressant and sleep drug, information about effects of agomelatine in PD are still lacking. Read More

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http://dx.doi.org/10.1016/j.neulet.2019.01.057DOI Listing
February 2019
1 Read
2.055 Impact Factor

L-DOPA modulates brain iron, dopaminergic neurodegeneration and motor dysfunction in iron overload and mutant alpha-synuclein mouse models of Parkinson's disease.

J Neurochem 2019 Feb 4. Epub 2019 Feb 4.

Melbourne Dementia Research Centre at The Florey Institute of Neuroscience and Mental Health and The University of Melbourne, Parkville, Victoria, Australia.

Treatment with the dopamine (DA) precursor L-3,4-dihydroxyphenylalanine (L-DOPA) provides symptomatic relief arising from DA denervation in Parkinson's disease. Mounting evidence that DA autooxidation to neurotoxic quinones is involved in Parkinson's disease pathogenesis has raised concern about potentiation of oxidative stress by L-DOPA. The rate of DA quinone formation increases in the presence of excess redox-active iron (Fe), which is a pathological hallmark of Parkinson's disease. Read More

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http://dx.doi.org/10.1111/jnc.14676DOI Listing
February 2019
4 Reads

Spatial distribution of multiple sclerosis lesions in the cervical spinal cord.

Brain 2019 Jan 30. Epub 2019 Jan 30.

NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. Read More

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https://academic.oup.com/brain/advance-article/doi/10.1093/b
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http://dx.doi.org/10.1093/brain/awy352DOI Listing
January 2019
4 Reads
9.196 Impact Factor

Depression and risk of Cognitive Dysfunctions in Amyotrophic Lateral Sclerosis.

Acta Neurol Scand 2019 Feb 3. Epub 2019 Feb 3.

Department of Neurology, University of Piemonte Orientale, Maggiore della Carità Hospital, Novara, Italy.

Objectives: ALS is not only a motor disorder: more than 50% of patients have cognitive dysfunctions over the course of the disease. At the same time, mood disorders may also occur in ALS patients following diagnosis due to the fatal prognosis; however little data is available on any depression beforehand. Starting from these considerations, the aim of our study was to investigate the occurrence of depression in Italian ALS patients prior to diagnosis, evaluating its prevalence in the subjects who have developed cognitive dysfunctions and in those who did not. Read More

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http://doi.wiley.com/10.1111/ane.13073
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http://dx.doi.org/10.1111/ane.13073DOI Listing
February 2019
3 Reads

Assisted ventilation in motor neurone disease during inpatient palliative care: barriers and utilisation.

BMJ Support Palliat Care 2019 Feb 2. Epub 2019 Feb 2.

Palliative Medicine, Velindre Cancer Centre, Cardiff, UK.

Objectives: An increasing number of patients with motor neuron disease (MND) in the UK and Ireland use assisted ventilation, and a small proportion of these use long-term tracheostomy ventilation (TV).1 2 NICE guidelines recommend that patients with MND should routinely receive specialist palliative care input.3 The aim was to establish the extent to which hospices and specialist palliative care units (SPCUs) in the UK and Ireland currently manage patients with MND using assisted ventilation especially TV and to identify any associated barriers. Read More

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http://dx.doi.org/10.1136/bmjspcare-2018-001672DOI Listing
February 2019
1 Read

Spike and Local Field Synchronization between the Pedunculopontine Nucleus and Primary Motor Cortex in a Rat Model of Parkinson's Disease.

Neuroscience 2019 Jan 30. Epub 2019 Jan 30.

Key Laboratory of Animal Resistance of Shandong Province, College of Life Science, Shandong Normal University, Jinan 250014, People's Republic of China. Electronic address:

The pedunculopontine nucleus (PPN) shows altered electrophysiological and anatomic characteristics in Parkinson's disease (PD), but little is known about the effect of 6- hydroxydopamine (6-OHDA) lesion and levodopa (-DOPA) therapy on the relationship between spike and local field potential (LFP) activities in the PPN and motor cortex. Aiming to investigate this, synchronous spike and LFP signals in the PPN and primary motor cortex (M1) were recorded. The spike-LFP relationship was evaluated using coherence analysis, phase-lock and spike-field coherence (SFC). Read More

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http://dx.doi.org/10.1016/j.neuroscience.2019.01.044DOI Listing
January 2019

Amyotrophic lateral sclerosis diagnostic index: Toward a personalized diagnosis of ALS.

Neurology 2019 Feb 11;92(6):e536-e547. Epub 2019 Jan 11.

From Westmead Clinical School (N.G., P.M., M.v.d.B., S.V.), Brain and Mind Center (J.H., K.S., J.M.M., S.B.P., M.C.K.), and NHMRC Clinical Trials Centre (K.B.), University of Sydney; and Westmead Hospital (K.B.), Research and Education Network, Sydney, Australia.

Objective: The aim of the study was to assess the utility of a novel amyotrophic lateral sclerosis (ALS) diagnostic index (ALSDI).

Methods: A prospective multicenter study was undertaken on patients presenting with suspected ALS. The reference standard (Awaji criteria) was applied to all patients at recruitment. Read More

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http://dx.doi.org/10.1212/WNL.0000000000006876DOI Listing
February 2019
2 Reads
8.286 Impact Factor

A rapidly progressive motor neuron disease associated to a natural killer cells leukaemia.

J Neurol Sci 2019 Jan 17;398:117-118. Epub 2019 Jan 17.

IRCCS Centro Neurolesi Bonino Pulejo, Palermo, Italy.

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http://dx.doi.org/10.1016/j.jns.2019.01.029DOI Listing
January 2019

Clinical and neuroimaging investigations of language disturbance in frontotemporal dementia-motor neuron disease patients.

J Neurol 2019 Feb 1. Epub 2019 Feb 1.

Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.

This study systematically investigated the neuropsychological profile of language disturbance in frontotemporal dementia-motor neuron disease (FTD-MND) using a data-driven approach. Neuroanatomical correlates of language profiles were also examined. Patients with FTD-MND (N = 26), pure motor neuron disease (N = 34), progressive non-fluent aphasia (N = 30), semantic dementia (N = 17), and controls (N = 31) underwent comprehensive language assessments. Read More

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http://dx.doi.org/10.1007/s00415-019-09216-0DOI Listing
February 2019
1 Read

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Neurologic Illnesses.

J Palliat Med 2019 Feb;22(2):193-198

5 Perelman School of Medicine and Palliative and Advanced Illness Research Center, University of Pennsylvania, Philadelphia, Pennsylvania.

Patients with neurologic illnesses are commonly encountered by palliative care (PC) clinicians though many clinicians feel uncomfortable caring for these patients. Understanding how to diagnose, treat, communicate with, and prognosticate for neurology patients will improve the confidence and competence of PC providers in the neurology setting. This article offers PC providers 10 useful tips that neurologists with PC training think all PC providers should know to improve care for patients with neurologic illness. Read More

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https://www.liebertpub.com/doi/10.1089/jpm.2018.0617
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http://dx.doi.org/10.1089/jpm.2018.0617DOI Listing
February 2019
5 Reads

Neurodegeneration and the Intersubjectivities of Care.

Med Anthropol 2019 Feb 1:1-15. Epub 2019 Feb 1.

b School of Healthcare Sciences , Cardiff University , Cardiff , United Kingdom.

Caring for a family member or friend with a serious health condition is a common feature of social life. Often, such care is framed as a burden, an unwelcome rupture in the fabric of everyday life. We draw on research conducted in Australia and the UK to examine care in the everyday lives of people living with and caring for neurodegenerative diseases and to trouble care as a burden. Read More

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http://dx.doi.org/10.1080/01459740.2019.1570189DOI Listing
February 2019

MAP4K4 Activation Mediates Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis.

Cell Rep 2019 Jan;26(5):1143-1156.e5

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons (MNs). To date, its underlying mechanisms have yet to be clarified completely, and there are no truly effective treatments. Here, we show that MAP4K4, a MAP kinase family member, regulates MN death, with its suppression not only promoting survival but preventing neurite degeneration and decreasing mutant SOD1 levels through autophagy activation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247193002
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http://dx.doi.org/10.1016/j.celrep.2019.01.019DOI Listing
January 2019
8 Reads

Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis.

Brain 2019 Jan 28. Epub 2019 Jan 28.

Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, 385 Glossop Road, Sheffield, UK.

As clinical evidence supports a negative impact of dysfunctional energy metabolism on the disease progression in amyotrophic lateral sclerosis, it is vital to understand how the energy metabolic pathways are altered and whether they can be restored to slow disease progression. Possible approaches include increasing or rerouting catabolism of alternative fuel sources to supplement the glycolytic and mitochondrial pathways such as glycogen, ketone bodies and nucleosides. To analyse the basis of the catabolic defect in amyotrophic lateral sclerosis we used a novel phenotypic metabolic array. Read More

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http://dx.doi.org/10.1093/brain/awy353DOI Listing
January 2019
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The effects of rotenone on TH, BDNF and BDNF-related proteins in the brain and periphery: Relevance to early Parkinson's disease.

J Chem Neuroanat 2019 Jan 25;97:23-32. Epub 2019 Jan 25.

School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA 5000, Australia. Electronic address:

Loss of dopaminergic neurons in the substantia nigra (SN) is one of the pathological hallmarks in Parkinson's disease (PD). This neuron loss is accompanied by reduced protein and activity levels of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. Reduced nigral brain-derived neurotrophic factor (BDNF) has been postulated to contribute to the loss of nigral dopaminergic neurons in PD by causing a lack of trophic support. Read More

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

Neuroprotection by urate on the mutant hSOD1-related cellular and Drosophila models of amyotrophic lateral sclerosis: Implication for GSH synthesis via activating Akt/GSK3β/Nrf2/GCLC pathways.

Brain Res Bull 2019 Mar 26;146:287-301. Epub 2019 Jan 26.

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150001, PR China. Electronic address:

Oxidative stress has been considered as a principal mechanism of motor neuron death in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease which could be caused by dominant mutations in an antioxidant enzyme superoxide dismutase-1 (SOD1). The aim of the present study was to investigate the potential neuroprotective effects and mechanisms of urate, an important endogenous antioxidant and a biomarker of favorable ALS progression rates, in the mutant human SOD1-related cellular and Drosophila models of ALS. Our results showed that urate treatment provided neuroprotective effects as confirmed by enhanced survival, attenuated motor impairments, reduced oxidative damage and increased antioxidant defense in hSOD1-G85R-expressing Drosophila models of ALS. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03619230183060
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http://dx.doi.org/10.1016/j.brainresbull.2019.01.019DOI Listing
March 2019
2 Reads

Nerve ultrasound in dorsal root ganglion disorders: Smaller nerves lead to bigger insights.

Authors:
Nens van Alfen

Clin Neurophysiol 2019 Jan 19. Epub 2019 Jan 19.

Radboud University Medical Center, Department of Neurology and Clinical Neurophysiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2019.01.004DOI Listing
January 2019

Impaired Pentose Phosphate Pathway in the Spinal Cord of the hSOD1 Mouse Model of Amyotrophic Lateral Sclerosis.

Mol Neurobiol 2019 Jan 26. Epub 2019 Jan 26.

Neurological Disorders and Metabolism Lab, School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.

Impairments in energy metabolism in amyotrophic lateral sclerosis (ALS) have long been known. However, the changes in the energy-producing pathways in ALS are not comprehensively understood. To investigate specific alterations in glucose metabolism in glycolytic, pentose phosphate, and TCA cycle pathways, we injected uniformly labeled [U-C]glucose to wild-type and hSOD1 mice at symptom onset (80 days). Read More

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http://dx.doi.org/10.1007/s12035-019-1485-6DOI Listing
January 2019
2 Reads

The Splicing Code Goes Deep.

Cell 2019 Jan;176(3):414-416

Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA. Electronic address:

The importance of genomic sequence context in generating transcriptome diversity through RNA splicing is independently unmasked by two studies in this issue (Jaganathan et al., 2019; Baeza-Centurion et al., 2019). Read More

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http://dx.doi.org/10.1016/j.cell.2019.01.013DOI Listing
January 2019

Dysregulated mitochondrial Ca and ROS signaling in skeletal muscle of ALS mouse model.

Arch Biochem Biophys 2019 Mar 22;663:249-258. Epub 2019 Jan 22.

Kansas City University of Medicine and Bioscience, Kansas City, MO 64106, USA; College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USA. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by motor neuron loss and prominent skeletal muscle wasting. Despite more than one hundred years of research efforts, the pathogenic mechanisms underlying neuromuscular degeneration in ALS remain elusive. While the death of motor neuron is a defining hallmark of ALS, accumulated evidences suggested that in addition to being a victim of motor neuron axonal withdrawal, the intrinsic skeletal muscle degeneration may also actively contribute to ALS disease pathogenesis and progression. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00039861183077
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http://dx.doi.org/10.1016/j.abb.2019.01.024DOI Listing
March 2019
3 Reads

Are we listening to everything the PARK genes are telling us?

J Comp Neurol 2019 Jan 24. Epub 2019 Jan 24.

Department of Neuroscience, Friedman Brain Institute and the Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai, New York, New York.

The cardinal motor symptoms that define Parkinson's disease (PD) clinically have been recognized for over 200 years. That these symptoms arise following the loss of dopamine neurons in the substantia nigra has been known for the last 50. These long-established facts have fueled a broadly held expectation that degenerating dopaminergic neurons alone hold the key to understanding and curing PD. Read More

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http://dx.doi.org/10.1002/cne.24642DOI Listing
January 2019
1 Read

Exploring Cerebrospinal Fluid IgG N-Glycosylation as Potential Biomarker for Amyotrophic Lateral Sclerosis.

Mol Neurobiol 2019 Jan 23. Epub 2019 Jan 23.

Institute of Physiology, Instituto de Medicina Molecular-Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which the existing candidate biomarkers (neurofilaments) have low specificity. Changes in blood IgG N-glycosylation have been observed in several diseases, including ALS, whereas cerebrospinal fluid (CSF) IgG has been less studied. Here, we characterized N-glycans of CSF IgG from ALS patients in comparison with a control group of other neurological diseases. Read More

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http://dx.doi.org/10.1007/s12035-019-1482-9DOI Listing
January 2019
4 Reads