Microglial cell-associated neuroinflammation is considered as a potential contributor to the pathophysiology of sporadic amyotrophic lateral sclerosis. However, the specific role of microglia in the disease pathogenesis remains to be elucidated. We studied the activation profiles of the microglial cultures exposed to the cerebrospinal fluid from these patients which recapitulates the neurodegeneration seen in sporadic amyotrophic lateral sclerosis. This was done by investigating the morphological and functional changes including the expression levels of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), TNF-α, IL-6, IFN-γ, IL-10, inducible nitric oxide synthase (iNOS), arginase, and trophic factors. We also studied the effect of chitotriosidase, the inflammatory protein found upregulated in the cerebrospinal fluid from amyotrophic lateral sclerosis patients, on these cultures. We report that the cerebrospinal fluid from amyotrophic lateral sclerosis patients could induce an early and potent response

Fingerprint Dive into the research topics of Immunoglobulins from animal models of motor neuron disease and from human amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction. Together they form a unique fingerprint. ...

TY - JOUR. T1 - Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. AU - Martinez, Hector R.. AU - Gonzalez-Garza, Maria T.. AU - Moreno-Cuevas, Jorge E.. AU - Caro, Enrique. AU - Gutierrez-Jimenez, Eugenio. AU - Segura, Jose J.. PY - 2009/1/1. Y1 - 2009/1/1. N2 - Background aims: Amyotrophic lateral sclerosis (ALS) is characterized by the selective death of motor neurons. CD133 + stem cells are known to have the capacity to differentiate into neural lineages. Stem cells may provide an alternative treatment for ALS and other neurodegenerative diseases. Methods: Five men and five women (aged 38-62 years) with confirmed ALS were included in this study. Our institutional ethics and research committees approved the protocol. After informed consent was obtained, patients underwent Hidrogen-Magnetic Resonance Imaging (H-MRI) spectroscopy and were given scores according to an ALS functional rating scale, Medical Research Council power muscle scale and ...

TY - JOUR. T1 - Activation of signal transducer and activator of transcription-3 in the spinal cord of sporadic amyotrophic lateral sclerosis patients. AU - Shibata, Noriyuki. AU - Kakita, Akiyoshi. AU - Takahashi, Hitoshi. AU - Ihara, Yuetsu. AU - Nobukuni, Keigo. AU - Fujimura, Harutoshi. AU - Sakoda, Saburo. AU - Sasaki, Shoichi. AU - Iwata, Makoto. AU - Morikawa, Shunichi. AU - Hirano, Asao. AU - Kobayashi, Makio. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2009/5. Y1 - 2009/5. N2 - Background: Neuroinflammation has been implicated in the pathomechanism of amyotrophic lateral sclerosis (ALS). It is known that signal transducer and activator of transcription-3 (STAT3) is a proinflammatory transcription factor. However, it remains to be determined whether STAT3 is involved in ALS. Objective: To test the hypothesis that STAT3 may be upregulated, activated, or both in the spinal cord of ALS patients. Methods: We performed immunohistochemical, immunoblot and ...

Amyotrophic lateral sclerosis (ALS), also referred to as Lou Gehrigs disease is a disease of the motor nerve cells in the brain and spinal cord. ALS is caused by progressive loss of motor nerves in these areas and affects approximately 1 out of 100,000 people. The diagnosis of ALS is usually based on clinical features, electrodiagnostic testing (EMG), and exclusion of other health conditions with related symptoms. Most people with amyotrophic lateral sclerosis have a form of the condition that is described as sporadic or noninherited. The cause of sporadic amyotrophic lateral sclerosis is largely unknown but probably involves a combination of genetic and environmental factors. About 10 percent of people with amyotrophic lateral sclerosis have a familial form of the condition, which is caused by an inherited genetic mutation ...

Recent metabolomic reports connect dysregulation of glycosphingolipids, particularly ceramide and glucosylceramide, to neurodegeneration and to motor unit dismantling in amyotrophic lateral sclerosis at late disease stage. We report here altered levels of gangliosides in the cerebrospinal fluid of amyotrophic lateral sclerosis patients in early disease stage. Conduritol B epoxide is an inhibitor of acid beta-glucosidase, and lowers glucosylceramide degradation. Glucosylceramide is the precursor for all of the more complex glycosphingolipids. In SOD1G86R mice, an animal model of amyotrophic lateral sclerosis, conduritol B epoxide preserved ganglioside distribution at the neuromuscular junction, delayed disease onset, improved motor function and preserved motor neurons as well as neuromuscular junctions from degeneration. Conduritol B epoxide mitigated gene dysregulation in the spinal cord and restored the expression of genes involved in signal transduction and axonal elongation. Inhibition of acid beta

Amyotrophic lateral sclerosis, or known as ALS, motor neuron disease, or upper and lower motor neuron disease, is a severe neurological disorder in brain and spinal cord that is characterized by disorders of voluntary muscle movement such as muscle weakness, permanent disability, until death. It is also called Lou Gehrigs disease because there was a basketball player named Lou Gehrig who died of this disease. Amyotrophic lateral sclerosis is a very uncommon disease who occurs at 5 of 100,000 people in the world. The risk exact causes of amyotrophic lateral sclerosis is still unknown, but generally it is a hereditary disease. Researchers also found that amyotrophic lateral sclerosis is caused by gene mutation, bad immune response, and chemical substance imbalance such as too much glutamate ...

Amyotrophic Lateral Sclerosis (ALS), Read about Amyotrophic Lateral Sclerosis (ALS) symptoms, causes, diagnosis, and treatment. Also read Amyotrophic Lateral Sclerosis (ALS) articles about how to live with Amyotrophic Lateral Sclerosis (ALS), and more.

BACKGROUND: Although an increasing role of genetic susceptibility has been recognized, the role of environmental risk factors in amyotrophic lateral sclerosis (ALS) etiology is largely uncertain; among neurotoxic chemicals, epidemiological and biological plausibility has been provided for pesticides, the heavy metal lead, the metalloid selenium, and other persistent organic pollutants. Selenium involvement in ALS has been suggested on the basis of epidemiological studies, in vitro investigations, and veterinary studies in which selenium induced a selective toxicity against motor neurons. OBJECTIVE: Hypothesizing a multistep pathogenic mechanism (genetic susceptibility and environmental exposure), we aimed to study selenium species in ALS patients carrying disease-associated gene mutations as compared to a series of hospital controls. METHODS: Using advanced analytical techniques, we determined selenium species in cerebrospinal fluid sampled at diagnosis in 9 ALS patients carrying different gene ...

Amyotrophic Lateral Sclerosis; Lou Gehrig Disease; Motor Neuron Disease, Amyotrophic Lateral Sclerosis. On-line free medical diagnosis assistant. Ranked list of possible diseases from either several symptoms or a full patient history. A similarity measure between symptoms and diseases is provided.

ObjectiveTo describe a mother who had autopsy-proved amyotrophic lateral sclerosis and her daughter who had clinically diagnosed Creutzfeldt-Jakob disease.Desig

Title: Molecular and Cellular Mechanism of Glutamate Receptors in Relation to Amyotrophic Lateral Sclerosis. VOLUME: 1 ISSUE: 5. Author(s): Yasuo Iwasaki, Ken Ikeda and Masao Kinoshita. Affiliation:Fourth Department of Internal Medicine, Toho University Ohashi Hospital, 2-17-6, Ohashi, Meguro-ku, Tokyo 153-8515, Japan.. Keywords:excitatory amino acids, glutamate, glutamate receptors, excitotoxicity, amyotrophic lateral sclerosis. Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of the central nervous system (CNS) with an unknown etiology. This disorder is characterized clinically by muscular weakness and wasting, and pathologically by selective degeneration of the corticospinal tracts and motor neurons of the brain stem and spinal cord. Median survival following onset is 3 to 5 years. Riluzole, an antiglutamatergic agent has been shown to have modest beneficial effects on survival. Glutamate is the main excitatory neurotransmitter in the CNS and excessive ...

TY - JOUR. T1 - Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England. AU - Andrew, Angeline S.. AU - Caller, Tracie A.. AU - Tandan, Rup. AU - Duell, Eric J.. AU - Henegan, Patricia L.. AU - Field, Nicholas C.. AU - Bradley, Walter G. AU - Stommel, Elijah W.. PY - 2017/2/1. Y1 - 2017/2/1. N2 - Background: Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS). Objective: To evaluate environmental and occupational exposures as risk factors for sporadic ALS. Methods: We performed a case-control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness. Results: Self-reported job-or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI ...

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Another name for Amyotrophic Lateral Sclerosis is Amyotrophic Lateral Sclerosis. The evaluation of amyotrophic lateral sclerosis begins with a history ...

Long interspersed element-1 (LINE-1/L1) is the only autonomous transposable element in the human genome that currently mobilises in both germline and somatic tissues. Recent studies have identified correlations between altered retrotransposon expression and the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) in a subset of patients. The risk of an individual developing ALS is dependent on an interaction of genetic variants and subsequent modifiers during life. These modifiers could include environmental factors, which can lead to epigenetic and genomic changes, such as somatic mutations, occurring in the neuronal cells that degenerate as the disease develops. There are more than 1 million L1 copies in the human genome today, but only 80-100 L1 loci in the reference genome are considered to be retrotransposition-competent (RC) and an even smaller number of these RC-L1s loci are highly active. We hypothesise that RC-L1s could affect normal cellular function through their mutagenic

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome of unknown etiology that most commonly affects people in middle and high age. The hallmark of ALS is a progressive and simultaneous loss of upper and lower motor neurons in the central nervous system that leads to a progressive muscle atrophy, paralysis and death usually by respiratory failure. ALS is not a pure motor neuronal syndrome; it extends beyond the motor system and affects extramotor areas of the brain as well. The majority of the patients suffer from a sporadic ALS disease (SALS) while in at least ten percent the disease appears in a familial form (FALS). Mutations in the gene encoding the antioxidant enzyme superoxide dismutase-1 (SOD1) are the most common cause of FALS. More than 165 SOD1 mutations have been described, and these confer the enzyme a cytotoxic gain of function. Evidence suggests that the toxicity results from structural instability which makes the mutated enzyme prone to misfold and form ...

ALS is characterized by oxidative damage in the brain and cerebrospinal fluid, which is exerted by pro-oxidative activity of iron. Such activity of iron can be drastically increased in the presence of inappropriate iron ligands that catalyze redox cycling of iron, thereby promoting hydroxyl radical generation. The aim of our study was to determine the relative level of inappropriate iron ligands in the cerebrospinal fluid of ALS patients. To determine the levels of inappropriate iron ligands and redox activity of iron in cerebrospinal fluid (10 samples from ALS patients and 10 controls), we applied electron paramagnetic resonance spectroscopy. We have shown that cerebrospinal fluid of ALS patients comprises twofold increased level of inappropriate iron ligands, proportionally increasing iron redox activity and hydroxyl radical production compared to controls. In conclusion, our results strongly support the pro-oxidative/detrimental role of inappropriately chelated iron in ALS pathophysiology. ...

TY - JOUR. T1 - Dorfin prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase 1 in a neuronal cell model of familial amyotrophic lateral sclerosis. AU - Takeuchi, Hideyuki. AU - Niwa, Jun Ichi. AU - Hishikawa, Nozomi. AU - Ishigaki, Shinsuke. AU - Tanaka, Fumiaki. AU - Doyu, Manabu. AU - Sobue, Gen. PY - 2004/4. Y1 - 2004/4. N2 - Dorfin is a RING-finger type ubiquitin ligase for mutant superoxide dismutase 1 (SOD1) that enhances its degradation. Mutant SOD1s cause familial amyotrophic lateral sclerosis (FALS) through the gain of unelucidated toxic properties. We previously showed that the accumulation of mutant SOD1 in the mitochondria triggered the release of cytochrome c, followed by the activation of the caspase cascade and induction of neuronal cell death. In the present study, therefore, we investigated whether Dorfin can modulate the level of mutant SOD1 in the mitochondria and subsequent caspase activation. We showed that Dorfin significantly reduced the ...

Objective:. The goal of this study is to see whether patterns of cerebral cortex dysfunction differ in Primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS). The function of several regions of the cerebral cortex will be assessed by clinical, physiological, and neuropsychological tests. Magnetic resonance imaging will be carried out in a subset of patients to explore the correlation between functional and anatomical measures of these cortical areas.. Study Population:. 30 patients with Primary lateral sclerosis who meet the diagnostic criteria for PLS proposed by Pringle and 30 patients with ALS who fulfill the revised El Escorial criteria for probable or definite ALS.. 30 healthy volunteers will be studied to provide training and practice in using the rating scales and to provide age-matched controls for EEG and imaging studies.. Design:. A screening examination will be carried out under protocol 01-N-0145 to determine eligibility. Patients and caregivers will return for two ...

Recently, rare mutations in the TARDBP gene have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to characterize the genetic variability of the TARDBP gene in a cohort of Sardinian ALS patients. The coding region of the gene was analyzed in 97 unrelated patients previously tested negative for superoxide dismutase (SOD1) mutations. The p.Ala382Thr (c.1144G,A) mutation was found in 30 patients (30.9%). The mutation was predominant in familial ALS patients (FALS) as it was represented in 24 of 30 FALS cases (80%) (p , 0.0003). Six cases were apparently sporadic (9% of sporadic ALS patients). No further mutation of TARDBP was found in our cohort of ALS patients. Patients carrying the mutation showed spinal site of onset in 24 cases (80%), an average age at onset of 54.7 ± 11.1 years, not significantly different from patients not harboring TARDBP mutations (56.7 ± 9.6) and a female:male gender ratio of 1:1.1. The haplotype ...

Result Median survival with combined type onset (two regions simultaneously) was shorter (18 months) than with bulbar onset (26 months, p=0.01). The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. 5 year survival rate was 21% for lower limb onset, 18% for upper limb onset and 16% for bulbar onset. No patient with a rapid spread pattern (two regions within 3 months from onset) survived ,5 years. Early manifestations of bulbar symptoms within 1 year were associated with worse survival (p,0.001) although no significant difference in survival was seen between groups with and without bulbar symptoms (p=0.51). In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. Bulbar function remained preserved in 27%, lower limb function in 10% and upper limb function in 2.7%. ...

TY - JOUR. T1 - Reduced p75NTRexpression delays disease onset only in female mice of a transgenic model of familial amyotrophic lateral sclerosis. AU - Küst, B.M.. AU - Brouwer, N.. AU - Mantingh, I.J.. AU - Boddeke, H.W.G.M.. AU - Copray, J.C.V.M.. PY - 2003/6/1. Y1 - 2003/6/1. N2 - hSOD1 (G93A) transgenic mice develop pathological changes similar to those in patients with familial amyotrophic lateral sclerosis (FALS). In particular, the progressive degeneration of motoneurons is charactered in this mouse model. One feature of stressed motoneurons in ALS and the hSOD1 mice is the induction of the p75 neurotrophin receptor, which is thought, under certain circumstances, to be a death-signaling molecule. We have studied disease progression of hSOD1 (G93A) mice in the absence of the p75NTRreceptor and we monitored histological changes in the ventral spinal cord. Whereas female double transgenics showed prolonged survival, this effect was not observed in males. Improved survival in female mice was ...

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Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin : Dysfunction of alsin, particularly its putative Rab5 guanine-nucleotide-exchange factor activity, has been linked to one form of juvenile onset recessive familial amyotrophic lateral sclerosis (ALS2). Multiple lines of alsin knockout ( ALS2 -/- ) mice have been generated to model this disease. However, it remains elusive whether the Rab5-dependent endocytosis is altered in ALS2 -/- neurons. To

OBJECTIVE: To explore the value of diffusion tensor imaging applied to those specific cerebral white matter tracts consistently involved pathologically in amyotrophic lateral sclerosis as a source of prognostic biomarkers. DESIGN: Baseline clinical assessment and 3-T diffusion tensor imaging, repeated after approximately 6 months.Tract-based spatial statistics were used to assess voxel wise correlations of just the baseline diffusion tensor imaging indices with the progression rate (change in disability score/time interval) within the corticospinal tract and corpus callosum. PATIENTS: The study involved 21 patients with amyotrophic lateral sclerosis and 3 patients with primary lateral sclerosis. RESULTS: Correlation was observed between fractional anisotropy and progression rate for a region of the corticospinal tract spanning the posterior limb of the internal capsule, with a left hemisphere emphasis. Posterior limb of the internal capsule fractional anisotropy showed potential to distinguish those

OBJECTIVE: To explore the value of diffusion tensor imaging applied to those specific cerebral white matter tracts consistently involved pathologically in amyotrophic lateral sclerosis as a source of prognostic biomarkers. DESIGN: Baseline clinical assessment and 3-T diffusion tensor imaging, repeated after approximately 6 months.Tract-based spatial statistics were used to assess voxel wise correlations of just the baseline diffusion tensor imaging indices with the progression rate (change in disability score/time interval) within the corticospinal tract and corpus callosum. PATIENTS: The study involved 21 patients with amyotrophic lateral sclerosis and 3 patients with primary lateral sclerosis. RESULTS: Correlation was observed between fractional anisotropy and progression rate for a region of the corticospinal tract spanning the posterior limb of the internal capsule, with a left hemisphere emphasis. Posterior limb of the internal capsule fractional anisotropy showed potential to distinguish those

Probable helicase senataxin is an enzyme that in humans is encoded by the SETX gene. This gene encodes a protein named for its homology to the Sen1p protein of fungi which has RNA helicase activity encoded by a domain at the C-terminal end of the protein. The protein encoded by this gene contains a DNA/RNA helicase domain at its C-terminal end which suggests that it may be involved in both DNA and RNA processing. Mutations in this gene have been associated with Ataxia oculomotor apraxia type 2 (AOA2) and an autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS4). GRCh38: Ensembl release 89: ENSG00000107290 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000043535 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Chance PF, Rabin BA, Ryan SG, Ding Y, Scavina M, Crain B, Griffin JW, Cornblath DR (Apr 1998). Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. Am J Hum Genet. 62 (3): ...

BEVERLY EAVES PERDUE GOVERNOR AMYOTROPHIC LATERAL SCLEROSIS AWARENESS MONTH 2012 BY THE GOVERNOR OF THE STATE OF NORTH CAROLINA A PROCLAMATION WHEREAS, Amyotrophic Lateral Sclerosis (ALS) is better known as Lou Gehrigs disease; and WHEREAS, ALS is a fatal neurodegenerative disease characterized by degeneration of cell bodies of the upper and lower motor neurons in the gray matter of the anterior horns of the spinal cord; and WHEREAS, the initial symptom of ALS is weakness of the skeletal muscles, especially those of the extremities; and WHEREAS, as ALS progresses, the patient experiences difficulty in swallowing, talking and breathing; and WHEREAS, ALS eventually causes muscles to atrophy and the patient becomes a functional quadriplegic; and WHEREAS, because ALS does not affect mental capacity, patients remain alert and aware of loss of motor functions; and WHEREAS, there is no known cause, means of prevention or cure for ALS, and once diagnosed, patients succumb to the illness within two to ...

TY - JOUR. T1 - Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis. AU - Cannon, Ashley. AU - Fujioka, Shinsuke. AU - Rutherford, Nicola J.. AU - Ferman, Tanis Jill. AU - Broderick, Daniel F.. AU - Boylan, Kevin B.. AU - Graff Radford, Neill R. AU - Uitti, Ryan J.. AU - Rademakers, Rosa V. AU - Wszolek, Zbigniew K. AU - Dickson, Dennis W. PY - 2013/5/7. Y1 - 2013/5/7. N2 - Objective: We examined the clinical and pathologic phenotypes of GRN mutation carriers with the pathogenic A9D (g.26C,A) missense mutation. Methods: Three patients with GRN A9D mutations were evaluated clinically and came to autopsy with subsequent neuropathologic examination. Results: The clinical diagnoses of patients with GRN A9D mutations were amyotrophic lateral sclerosis, atypical extrapyramidal disorder, and behavioral variant frontotemporal dementia. Immunohistochemistry for TAR DNA-binding protein 43 (TDP-43) revealed variability in morphology and distribution of pathology. ...

We have found strong evidence of a genetic association of two single nucleotide polymorphisms on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS and linkage studies of ALS-frontotemporal dementia. Our findings together with these earlier findings suggest that genetic variation at this locus on chromosome 9 causes sporadic ALS and familial ALS-frontotemporal dementia. Resequencing studies and then functional analysis should be done to identify the defective gene.. ...

The early motor manifestations of sporadic amyotrophic lateral sclerosis (ALS), while rarely documented, reflect failure of adaptive complex motor skills. The development of these skills correlates with progressive evolution of a direct corticomotoneuronal system that is unique to primates and markedly enhanced in humans. The failure of this system in ALS may translate into the split hand presentation, gait disturbance, split leg syndrome and bulbar symptomatology related to vocalisation and breathing, and possibly diffuse fasciculation, characteristic of ALS. Clinical neurophysiology of the brain employing transcranial magnetic stimulation has convincingly demonstrated a presymptomatic reduction or absence of short interval intracortical inhibition, accompanied by increased intracortical facilitation, indicating cortical hyperexcitability. The hallmark of the TDP-43 pathological signature of sporadic ALS is restricted to cortical areas as well as to subcortical nuclei that are under the direct ...

Amyotrophic lateral sclerosis as a system failure is a concept supported by the finding of consistent extramotor as well as motor cerebral pathology. The functional correlates of the structural changes detected using advanced magnetic resonance imaging techniques such as diffusion tensor imaging and voxel-based morphometry have not been extensively studied. A group of 25 patients with amyotrophic lateral sclerosis was compared to healthy control subjects using a multi-modal neuroimaging approach comprising T(1)-weighted, diffusion-weighted and resting-state functional magnetic resonance imaging. Using probabilistic tractography, a grey matter connection network was defined based upon the prominent corticospinal tract and corpus callosum involvement demonstrated by white matter tract-based spatial statistics. This amyotrophic lateral sclerosis-specific network included motor, premotor and supplementary motor cortices, pars opercularis and motor-related thalamic nuclei. A novel analysis protocol, using

Amyotrophic lateral sclerosis as a system failure is a concept supported by the finding of consistent extramotor as well as motor cerebral pathology. The functional correlates of the structural changes detected using advanced magnetic resonance imaging techniques such as diffusion tensor imaging and voxel-based morphometry have not been extensively studied. A group of 25 patients with amyotrophic lateral sclerosis was compared to healthy control subjects using a multi-modal neuroimaging approach comprising T(1)-weighted, diffusion-weighted and resting-state functional magnetic resonance imaging. Using probabilistic tractography, a grey matter connection network was defined based upon the prominent corticospinal tract and corpus callosum involvement demonstrated by white matter tract-based spatial statistics. This amyotrophic lateral sclerosis-specific network included motor, premotor and supplementary motor cortices, pars opercularis and motor-related thalamic nuclei. A novel analysis protocol, using

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BACKGROUND. The genetic contribution to sporadic amyotrophic lateral sclerosis (ALS) has not been fully elucidated. There are increasing efforts to characterise the role of copy number variants (CNVs) in human diseases; two previous studies concluded that CNVs may influence risk of sporadic ALS, with multiple rare CNVs more important than common CNVs. A little-explored issue surrounding genome-wide CNV association studies is that of post-calling filtering and merging of raw CNV calls. We undertook simulations to define filter thresholds and considered optimal ways of merging overlapping CNV calls for association testing, taking into consideration possibly overlapping or nested, but distinct, CNVs and boundary estimation uncertainty.. METHODOLOGY AND PRINCIPAL FINDINGS. In this study we screened Illumina 300K SNP genotyping data from 730 ALS cases and 789 controls for copy number variation. Following quality control filters using thresholds defined by simulation, a total of 11321 CNV calls were ...

Amyotrophic lateral sclerosis (ALS) is a disease in which the motor neurons die in a progressive manner, leading to paralysis and muscle wasting. ALS is always fatal, usually through respiratory failure when the disease reaches muscles needed for breathing. Most cases are sporadic, but approximately 5-10% are familial. The first gene to be linked to familial ALS encodes the antioxidant enzyme superoxide dismutase-1 (SOD1). Today, more than 160 different mutations in SOD1 have been found in ALS patients. The mutant SOD1 proteins cause ALS by gain of a toxic property that should be common to all. Aggregates of SOD1 in motor neurons are hallmarks of ALS patients and transgenic models carrying mutant SOD1s, suggesting that misfolding, oligomerization, and aggregation of the protein may be involved in the pathogenesis. SOD1 is normally a very stable enzyme, but the structure has several components that make SOD1 sensitive to misfolding. The aim of the work in this thesis was to study misfolded SOD1 ...

Amyotrophic lateral sclerosis (ALS) is one of the progressive neurodegenerative disorders, affecting upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Hence, the signs of damage motor neurons are both at the peripheral (eg. atrophy), and central (eg. spasticity) level. There is no effective treatment for ALS and the majority of patients die within 5 years after diagnosis, usually due to respiratory failure. Numerous studies on murine models revealed that mesenchymal stem cells (MSCs) successfully improve the clinical and pathological features of ALS. The goal of this nonrandomized, open label study is to investigate the safety and tolerability of autologous bone marrow-derived mesenchymal stem cell transplantation into the individuals with diagnosed amyotrophic lateral sclerosis. This clinical trial is conducted to test the therapeutic (neuroprotective and paracrine) effect of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). All patients enrolled ...

TY - JOUR. T1 - Amyotrophic lateral sclerosis in pregnancy is associated with a vascular endothelial growth factor promoter genotype. AU - Lunetta, C.. AU - Sansone, V. A.. AU - Penco, S.. AU - Mosca, L.. AU - Tarlarini, C.. AU - Avemaria, F.. AU - Maestri, E.. AU - Melazzini, M. G.. AU - Meola, G.. AU - Corbo, M.. PY - 2014/4. Y1 - 2014/4. N2 - Background and purpose: The occurrence of amyotrophic lateral sclerosis (ALS) during pregnancy is uncommon and the effect of one on the other is not well described. Methods: The clinical and genetic features of five cases of ALS are reported with an onset during pregnancy or within 1 month from delivery. Charts from 239 women with a diagnosis of ALS attending the neuromuscular clinics at the Neuromuscular Omnicentre (NEMO) and at IRCCS Policlinico San Donato from 2008 to 2011 were reviewed. Results: Of these, 12.8% of the women in child-bearing age had a diagnosis of ALS during pregnancy or immediately after delivery. Genetic screening of the major ...

Major advance in genetic study of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) was identified by researchers in 2011.  A mutation known as a repeat expansion in an intron of the C9ORF72 gene was found to be the most important genetic risk factor for these disorders.  Most healthy people have 25 or fewer copies of the repeat, whereas mutation carriers can have 700 copies or more. The mutation explains roughly half of familial ALS cases and about a quarter of inherited FTLD, as well as some sporadic cases. However, scientists have since puzzled over how that mutation promotes disease. Researchers in Germany report in Science the surprising news that the intron expansions are translated into proteins. Being an expanded hexanucleotide repeat in an intron (i.e., non-coding region of DNA) the mutation should not affect the protein ...

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo. Abnormalities are detectable before clinical symptoms develop, offering the potential for neuroprotective intervention in familial cases. Although promising neuroimaging biomarker candidates for diagnosis, prognosis, and disease progression have emerged, these have been from the study of necessarily select patient cohorts identified in specialized referral centers. Further

Amyotrophic lateral sclerosis (ALS) is characterized by adult-onset progressive degeneration of upper and lower motor neurons. Increasing numbers of genes are found to be associated with ALS; among those, the first identified gene, SOD1 coding a Cu/Zn-superoxide dismutase protein (SOD1), has been regarded as the gold standard in the research on a pathomechanism of ALS. Abnormal accumulation of misfolded SOD1 in affected spinal motor neurons has been established as a pathological hallmark of ALS caused by mutations in SOD1 (SOD1-ALS). Nonetheless, involvement of wild-type SOD1 remains quite controversial in the pathology of ALS with no SOD1 mutations (non-SOD1 ALS), which occupies more than 90% of total ALS cases. In vitro studies have revealed post-translationally controlled misfolding and aggregation of wild-type as well as of mutant SOD1 proteins; therefore, SOD1 proteins could be a therapeutic target not only in SOD1-ALS but also in more prevailing cases, non-SOD1 ALS. In order to search for evidence

Amyotrophic lateral sclerosis (ALS) is a devastating neurological syndrome in which motor neurons degenerate relentlessly. Although the site of onset and the rate of spread have been studied extensively, little is known about whether focal as opposed to diffuse disease affects prognosis. We therefore tested the hypothesis that regionality of disease burden is a prognostic factor in ALS. We analysed clinical data from two large multicentre, longitudinal trials. Regionality was defined as the difference in progression rates in three domains as measured by the revised ALS Functional Rating Scale, omitting the respiratory domain from analysis. We used death by trial end as the outcome variable and tested this by logistic regression against predictor variables including regionality and overall rate of disease progression. There were 561 patients. Regionality of disease was independently associated with significantly higher chance of death by study end (odds ratio most diffuse against most focal category 0

TY - JOUR. T1 - Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes. AU - Gorter, R. P.. AU - Stephenson, J.. AU - Nutma, E.. AU - Anink, J.. AU - de Jonge, J. C.. AU - Baron, W.. AU - Jahreiss, M. -C.. AU - Belien, J. A. M.. AU - van Noort, J. M.. AU - Mijnsbergen, C.. AU - Aronica, E.. AU - Amor, S.. N1 - This article is protected by copyright. All rights reserved.. PY - 2019/8. Y1 - 2019/8. N2 - AIMS: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterised by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2-5 years of onset. Neuroinflammation is a hallmark of ALS pathology characterized by activation of glial cells, which respond by upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated the association between ALS ...

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrigs disease, is a rare disease with extreme between-subject variability, especially with respect to rate of disease progression. This makes modelling a subjects disease progression, which is measured by the ALS Functional Rating Scale (ALSFRS), very difficult. Consider the problem of predicting a subjects ALSFRS score at 9 or 12 months after a given time-point. We obtained ALS subject data from the Pooled Resource Open-Access ALS Clinical Trials Database, a collection of data from various ALS clinical trials. Due to the typical linearity of the ALSFRS, we consider several Bayesian hierarchical linear models. These include a mixture model (to account for the two potential classes of

Title:Metallothionein is a Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis. VOLUME: 23 ISSUE: 33. Author(s):Shin-ichi Ono*. Affiliation:Laboratory of Clinical Medicine, School of Pharmacy, Nihon University, 7-1, 7-chome, Narashinodai, Funabashi, Chiba 274-8555. Keywords:Metallothionein, intracellular Cu homeostasis, SOD1 mutation, cysteine111, Cu chaperons, Cu secretion.. Abstract:Lou Gehrigs disease, a synonym of amyotrophic lateral sclerosis, is an adult-onset lethal neurodegenerative disorder. Irrespective of extensive efforts to elucidate the pathogenesis of the disease and searches for therapies, no favorable pharmacotherapeutic strategies have yet to be proposed. In a popular rodent model of ALS, G93A SOD1 strain of mouse, intracellular copper conditions were geared toward copper accumulation inside cells, resulting in an acceleration of oxidative stress and apoptotic process. Disruption of intracellular copper homeostasis was common to transgenic mice expressing human ...

What is amyotrophic lateral sclerosis? Amyotrophic lateral sclerosis, or ALS, is a disease in which certain nerve cells in the brain and spinal cord slowly die. These nerve cells are called motor neurons, and they control the muscles that allow you to move the parts of your body. ALS is also called Lou Gehrigs...

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. OBJECTIVE: The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. DESIGN: The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. PARTICIPANTS: Eligible participants had a diagnosis of ALS (ALS ...

Amyotrophic lateral sclerosis definition is - a rare progressive degenerative fatal disease affecting the motor neurons, usually beginning in middle age, and characterized especially by increasing and spreading muscular weakness and atrophy -abbreviation ALS-called also Lou Gehrigs disease.