27,178 results match your criteria Amyotrophic lateral sclerosis & frontotemporal degeneration[Journal]


Common mutations of interest for the diagnosis of amyotrophic lateral sclerosis: how common are common mutations in ALS genes?

Expert Rev Mol Diagn 2020 Jun 4. Epub 2020 Jun 4.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria , Rende (Cosenza), Italy.

Introduction: Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease predominantly affecting upper and lower motor neurons. Diagnosis of this devastating pathology is very difficult because the high degree of clinical heterogeneity with which it occurs and until now, no truly effective treatment exists. Areas covered: Molecular diagnosis may be a valuable tool for dissecting out ALS complex heterogeneity and for identifying new molecular mechanisms underlying the characteristic selective degeneration and death of motor neurons. Read More

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http://dx.doi.org/10.1080/14737159.2020.1779060DOI Listing

AMYOTROPHIC LATERAL SCLEROSIS, CANCER, AUTOIMMUNITY AND METABOLIC DISORDERS: AN UNSOLVED TANTALIZING CHALLENGE.

Br J Pharmacol 2020 Jun 4. Epub 2020 Jun 4.

Centro de Investigación en Red de Enfermedades Neurodegenerativas, CIBERNED. Instituto Carlos III, Madrid, Spain.

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown pathogenesis that progresses rapidly, has attracted an increased amount of scholarly interest in recent years. The current conception of ALS has transitioned into a more complex theory in which individual genetic risk, ageing, and environmental factors interact, leading to disease onset in subjects in whom the sum of these factors reach a determined threshold. Based on this conceptualization, the environmental conditions, particularly those that are potentially modifiable, are becoming increasingly relevant. Read More

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http://dx.doi.org/10.1111/bph.15151DOI Listing

Excessive Homeostatic Gain in Spinal Motoneurons in a Mouse Model of Amyotrophic Lateral Sclerosis.

Sci Rep 2020 Jun 3;10(1):9049. Epub 2020 Jun 3.

Department of Physiology, Northwestern University, Chicago, IL, 60611, USA.

In the mSOD1 model of ALS, the excitability of motoneurons is poorly controlled, oscillating between hyperexcitable and hypoexcitable states during disease progression. The hyperexcitability is mediated by excessive activity of voltage-gated Na and Ca channels that is initially counteracted by aberrant increases in cell size and conductance. The balance between these opposing actions collapses, however, at the time that the denervation of muscle fibers begins at about P50, resulting in a state of hypo-excitability and cell death. Read More

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http://dx.doi.org/10.1038/s41598-020-65685-8DOI Listing

S100A6 and Its Brain Ligands in Neurodegenerative Disorders.

Int J Mol Sci 2020 Jun 1;21(11). Epub 2020 Jun 1.

Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.

The S100A6 protein is present in different mammalian cells and tissues including the brain. It binds Ca and Zn and interacts with many target proteins/ligands. The best characterized ligands of S100A6, expressed at high level in the brain, include CacyBP/SIP and Sgt1. Read More

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http://dx.doi.org/10.3390/ijms21113979DOI Listing

Hardy-Weinberg Equilibrium in different mitochondrial haplogroups of four genes associated with neuroprotection and neurodegeneration.

Arq Neuropsiquiatr 2020 May 29;78(5):269-276. Epub 2020 May 29.

Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Background: Malfunctioning or damaged mitochondria result in altered energy metabolism, redox equilibrium, and cellular dynamics and is a central point in the pathogenesis of neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis. Therefore, it is of utmost importance to identify mitochondrial genetic susceptibility markers for neurodegenerative diseases. Potential markers include the respiratory chain enzymes Riboflavin kinase (RFK), Flavin adenine dinucleotide synthetase (FAD), Succinate dehydrogenase B subunit (SDHB), and Cytochrome C1 (CYC1). Read More

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http://dx.doi.org/10.1590/0004-282x20200002DOI Listing

Differential regulation of TREM2 and CSF1R in CNS macrophages in an SIV/macaque model of HIV CNS disease.

J Neurovirol 2020 Jun 2. Epub 2020 Jun 2.

Department of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.

HIV-associated neuroinflammation is primarily driven by CNS macrophages including microglia. Regulation of these immune responses, however, remains to be characterized in detail. Using the SIV/macaque model of HIV, we evaluated CNS expression of triggering receptor expressed on myeloid cells 2 (TREM2) which is constitutively expressed by microglia and contributes to cell survival, proliferation, and differentiation. Read More

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http://dx.doi.org/10.1007/s13365-020-00844-1DOI Listing

Nationwide survey of 780 Japanese patients with amyotrophic lateral sclerosis: their status and expectations from brain-machine interfaces.

J Neurol 2020 Jun 1. Epub 2020 Jun 1.

Department of Neurological Diagnosis and Restoration, Osaka University Graduate School of Medicine, CoMIT, 2-2 Yamadaoka, Suita, Osaka, 913A565-0871, Japan.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes eventual death through respiratory failure unless mechanical ventilation is provided. Brain-machine interfaces (BMIs) may provide brain control supports for communication and motor function. We investigated the interests and expectations of patients with ALS concerning BMIs based on a large-scale anonymous questionnaire survey supported by the Japan Amyotrophic Lateral Sclerosis Association. Read More

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http://dx.doi.org/10.1007/s00415-020-09903-3DOI Listing

From basic research to the clinic: innovative therapies for ALS and FTD in the pipeline.

Mol Neurodegener 2020 Jun 1;15(1):31. Epub 2020 Jun 1.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149, Trieste, Italy.

Amyotrophic lateral sclerosis (ALS) and Frontotemporal Degeneration (FTD) are neurodegenerative disorders, related by deterioration of motor and cognitive functions and short survival. Aside from cases with an inherited pathogenic mutation, the causes of the disorders are still largely unknown and no effective treatment currently exists. It has been shown that FTD may coexist with ALS and this overlap occurs at clinical, genetic, and molecular levels. Read More

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http://dx.doi.org/10.1186/s13024-020-00373-9DOI Listing

Molecular Targets from Traditional Medicines for Neuroprotection in Human Neurodegenerative Diseases.

OMICS 2020 Jun 2. Epub 2020 Jun 2.

Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India.

Neurodegeneration is one of the greatest threats to global public health. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are among the major causes of chronic neurological conditions in the elderly populations. Hence, neuroprotection is at the epicenter of the current 21st-century research agenda in biomedicine. Read More

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http://dx.doi.org/10.1089/omi.2020.0033DOI Listing

Decline of cognitive and behavioral functions in amyotrophic lateral sclerosis: a longitudinal study.

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 2:1-7. Epub 2020 Jun 2.

ALS Center, Department of Neurology, Azienda Ospedaliera Universitaria Maggiore della Carità, Novara, Italy.

: A cognitive impairment, ranging from frontotemporal dementia (FTD) to milder forms of dysexecutive or behavioral dysfunction, is detected in 30-50% of patients affected by amyotrophic lateral sclerosis (ALS) at diagnosis. Such condition considerably influences the prognosis, and possibly impacts on the decision-making process with regards to end-of-life choices. The aim of our study is to examine the changes of cognitive and behavioral impairment in a large population of ALS from the time of diagnosis to a 6-month follow-up (IQR 5. Read More

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http://dx.doi.org/10.1080/21678421.2020.1771732DOI Listing

The involvement of regulatory T cells in amyotrophic lateral sclerosis and their therapeutic potential.

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 2:1-10. Epub 2020 Jun 2.

Sheffield Institute of Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, Sheffield, UK.

Neuroinflammation, meaning the establishment of a diffuse inflammatory condition in the CNS, is one of the main hallmarks of amyotrophic lateral sclerosis (ALS). Recently, a crucial role of regulatory T cells (Tregs) in this disease has been outlined. Tregs are a T cell subpopulation with immunomodulatory properties. Read More

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http://dx.doi.org/10.1080/21678421.2020.1752246DOI Listing

Synaptic restoration by cAMP/PKA drives activity-dependent neuroprotection to motoneurons in ALS.

J Exp Med 2020 Aug;217(8)

Université de Paris, Saints-Pères Paris Institute for the Neurosciences (SPPIN), Centre National de la Recherche Scientifique (CNRS), Paris, France.

Excessive excitation is hypothesized to cause motoneuron (MN) degeneration in amyotrophic lateral sclerosis (ALS), but actual proof of hyperexcitation in vivo is missing, and trials based on this concept have failed. We demonstrate, by in vivo single-MN electrophysiology, that, contrary to expectations, excitatory responses evoked by sensory and brainstem inputs are reduced in MNs of presymptomatic mutSOD1 mice. This impairment correlates with disrupted postsynaptic clustering of Homer1b, Shank, and AMPAR subunits. Read More

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http://dx.doi.org/10.1084/jem.20191734DOI Listing

Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature.

Ann Pharmacother 2020 Jun 2:1060028020930189. Epub 2020 Jun 2.

Intermountain Healthcare, Taylorsville, UT, USA.

To compile and synthesize the available literature describing medical cannabis use across various disease states. PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. Read More

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http://dx.doi.org/10.1177/1060028020930189DOI Listing

Young-onset Amyotrophic Lateral Sclerosis with Rare Skin Manifestation: Case Report and Literature Review.

Cureus 2020 Apr 27;12(4):e7844. Epub 2020 Apr 27.

Medicine, Dow University of Health Sciences, Karachi, PAK.

Amyotrophic lateral sclerosis (ALS) is one of the most common motor neuron diseases (MND), which presents as muscle weakness, atrophy, spasticity, and, in extreme cases, may result in death due to respiratory failure. ALS has been reported with dermatological conditions such as bullous pemphigoid and decreased collagen. Hyperpigmentation usually occurs due to underlying adrenal or metabolic disorder, but no case of hyperpigmentation has been associated with MND. Read More

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http://dx.doi.org/10.7759/cureus.7844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253073PMC

C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.

Nature 2020 Jun 13;582(7810):89-94. Epub 2020 May 13.

Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins before its non-canonical translation into neural-toxic dipeptide proteins. Read More

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http://dx.doi.org/10.1038/s41586-020-2288-7DOI Listing

Tamoxifen for amyotrophic lateral sclerosis: A randomized double-blind clinical trial.

Medicine (Baltimore) 2020 May;99(22):e20423

Neurology Department, Shuang-Ho Hospital.

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common cause of motor neuron disease, and effective treatment for ALS is still lacking. Transactive response (TAR) -DNA-binding protein-43 (TDP-43) is aggregated in the neurons of ALS patients. Animal studies shown TDP-43 aggregation can be attenuated by enhancing autophagy by tamoxifen. Read More

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http://dx.doi.org/10.1097/MD.0000000000020423DOI Listing

Hypoglossal Nerve: Anatomy, Anatomical Variations Comorbidities and Clinical Significance.

J Long Term Eff Med Implants 2019 ;29(3):197-203

Department of Anatomy and Surgical Anatomy, Medical School of National and Kapodistrian University of Athens, Athens, Greece.

We review the anatomical variations of the hypoglossal nerve and their surgical and clinical significance, and we report multiple diseases that affect function of the nerve leading to paresis, either unilateral or bilateral. The hypoglossal nerve is the 12th cranial nerve, and knowledge of the detailed anatomy and relationship with critical structures is of paramount importance in neurosurgery, head and neck surgery, and vascular surgery. Numerous studies have depicted conventional landmarks in the cervical part of the hypoglossal nerve, but their findings have not been consistent reliable. Read More

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http://dx.doi.org/10.1615/JLongTermEffMedImplants.2020033230DOI Listing
January 2019

FUS ALS-causative mutations impair FUS autoregulation and splicing factor networks through intron retention.

Nucleic Acids Res 2020 Jun 1. Epub 2020 Jun 1.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.

Mutations in the RNA-binding protein FUS cause amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease. FUS plays a role in numerous aspects of RNA metabolism, including mRNA splicing. However, the impact of ALS-causative mutations on splicing has not been fully characterized, as most disease models have been based on overexpressing mutant FUS, which will alter RNA processing due to FUS autoregulation. Read More

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http://dx.doi.org/10.1093/nar/gkaa410DOI Listing

Umbilical cord-derived mesenchymal stem cells in neurodegenerative disorders: from literature to clinical practice.

Regen Med 2020 Jun 1. Epub 2020 Jun 1.

Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran 14177-44361, Iran.

Mesenchymal stem cells (MSCs) have provided a promising tool for cell therapy. Umbilical cord (UC) is one of the best sources of MSCs since its collection is noninvasive, and effortless, and the cells from this source are more capable and prolific. It has been proven that the differentiation, migration and protective properties of UC-MSCs are superior compared with other kinds of stem cells. Read More

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http://dx.doi.org/10.2217/rme-2019-0119DOI Listing

Spinal Cord Microglia in Health and Disease.

Acta Naturae 2020 Jan-Mar;12(1):4-17

Institute of Experimental Medicine, St. Petersburg, 197376 Russia.

The review summarizes data of recent experimental studies on spinal microglia, the least explored cells of the spinal cord. It focuses on the origin and function of microglia in mammalian spinal cord embryogenesis. The main approaches to the classification of microgliocytes based on their structure, function, and immunophenotypic characteristics are analyzed. Read More

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http://dx.doi.org/10.32607/actanaturae.10934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245960PMC

Cytoplasmic TDP43 Binds microRNAs: New Disease Targets in Amyotrophic Lateral Sclerosis.

Front Cell Neurosci 2020 12;14:117. Epub 2020 May 12.

Department of Neurology, University of Michigan, Ann Arbor, MI, United States.

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, and incurable neurodegenerative disease. Recent studies suggest that dysregulation of gene expression by microRNAs (miRNAs) may play an important role in ALS pathogenesis. The reversible nature of this dysregulation makes miRNAs attractive pharmacological targets and a potential therapeutic avenue. Read More

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http://dx.doi.org/10.3389/fncel.2020.00117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235295PMC

The epidemiology of amyotrophic lateral sclerosis in Moscow (Russia).

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 1:1-6. Epub 2020 Jun 1.

Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.

: To estimate the incidence of amyotrophic lateral sclerosis (ALS) in Moscow by investigating multiple sources of cases. Incidence rates from previous Russian studies ranged from 0.3 to 0. Read More

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http://dx.doi.org/10.1080/21678421.2020.1752252DOI Listing

Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs.

Mol Neurobiol 2020 May 30. Epub 2020 May 30.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr., Raleigh, NC, 27607, USA.

Age is a primary risk factor for multiple comorbidities including neurodegenerative diseases. Pet dogs and humans represent two populations that have experienced a significant increase in average life expectancy over the last century. A higher prevalence of age-related neurodegenerative diseases has been observed across both species, and human diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), have canine analogs, canine cognitive dysfunction (CCD), and degenerative myelopathy (DM) respectively. Read More

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http://dx.doi.org/10.1007/s12035-020-01951-0DOI Listing

Caffeine and NAD Improve Motor Neural Integrity of Dissociated Wobbler Cells In Vitro.

Antioxidants (Basel) 2020 May 27;9(6). Epub 2020 May 27.

Department of Cytology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, D-44801 Bochum, Germany.

Amyotrophic lateral sclerosis (ALS) is a common degenerative disease of the central nervous system concerning a progressive loss of upper and lower motor neurons. While 5%-10% of patients are diagnosed with the inherited form of the disease, the vast majority of patients suffer from the less characterized sporadic form of ALS (sALS). As the wobbler mouse and the ALS show striking similarities in view of phenotypical attributes, the mouse is rated as an animal model for the disease. Read More

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http://dx.doi.org/10.3390/antiox9060460DOI Listing

CRISPR/Cas9-Mediated Gene Correction to Understand ALS.

Authors:
Yeomin Yun Yoon Ha

Int J Mol Sci 2020 May 27;21(11). Epub 2020 May 27.

Department of Neurosurgery, Spine and Spinal Cord Institute, College of Medicine, Yonsei University, Seoul 03722, Korea.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the death of motor neurons in the spinal cord and brainstem. ALS has a diverse genetic origin; at least 20 genes have been shown to be related to ALS. Most familial and sporadic cases of ALS are caused by variants of the , , and TARDBP genes. Read More

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http://dx.doi.org/10.3390/ijms21113801DOI Listing

Intrusion errors during verbal fluency task in amyotrophic lateral sclerosis.

PLoS One 2020 29;15(5):e0233349. Epub 2020 May 29.

Department of Neurology, Basurto University Hospital, Vizcaya, Spain.

Background: Numerous studies have noted the presence of a dysexecutive component of the ALS-FTD. The most widely replicated result refers to the significantly reduced verbal fluency of ALS patients when compared to healthy people. As ALS patients have motor alterations that interfere with production, qualitative studies have the advantage of being independent of the degree of motor disability and revealing patients' cognitive state. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233349PLOS

Targeting TDP-43 proteinopathy with drugs and drug-like small molecules.

Authors:
Emanuele Buratti

Br J Pharmacol 2020 May 29. Epub 2020 May 29.

International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149, Trieste, Italy.

Following the discovery of TDP-43 involvement in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) a major research focus has been to develop treatments that can prevent or alleviate disease conditions. From a pharmacological point of view, one approach has been to use TDP-43 based disease-models to test small molecules and drugs already known to have some therapeutic effect in a variety of neurodegenerative conditions. In parallel, various disease models have been used to perform high-throughput screens of drugs and small compound libraries. Read More

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http://dx.doi.org/10.1111/bph.15148DOI Listing

Tetrodotoxin-Sensitive Neuronal-Type Na Channels: A Novel and Druggable Target for Prevention of Atrial Fibrillation.

J Am Heart Assoc 2020 Jun 29;9(11):e015119. Epub 2020 May 29.

Dorothy M. Davis Heart and Lung Research Institute College of Medicine The Ohio State University Wexner Medical Center Columbus OH.

Background Atrial fibrillation (AF) is a comorbidity associated with heart failure and catecholaminergic polymorphic ventricular tachycardia. Despite the Ca-dependent nature of both of these pathologies, AF often responds to Na channel blockers. We investigated how targeting interdependent Na/Ca dysregulation might prevent focal activity and control AF. Read More

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http://dx.doi.org/10.1161/JAHA.119.015119DOI Listing

Overexpression of NDRG2 in skeletal muscle does not ameliorate the effects of stress in vivo.

Exp Physiol 2020 May 29. Epub 2020 May 29.

Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.

New Findings: What is the central question of this study? Do elevated levels of the stress-response NDRG2 protein protect against fasting and chronic disease in mouse skeletal muscle? What is the main finding and its importance? NDRG2 levels increased in response to fasting and motor neurone disease effects in the tibialis anterior muscle. No alleviation of the stress-related and proteasomal pathways, mitochondrial dysfunction or muscle mass loss was observed even with further exogenous NDRG2 added indicating that the increased NDRG2 in skeletal muscle is simply a normal adaptive response.

Abstract: Skeletal muscle mass loss and dysfunction can arise from stress leading to enhanced protein degradation and metabolic impairment. Read More

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http://dx.doi.org/10.1113/EP088620DOI Listing

Detecting Common Pathways and Key Molecules of Neurodegenerative Diseases from the Topology of Molecular Networks.

Adv Exp Med Biol 2020 ;1194:409-421

Department of Informatics, Ionian University, Corfu, Greece.

MotivationNeurodegenerative diseases (NDs), including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease, occur as a result of neurodegenerative processes. Thus, it has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels. However, traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Read More

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http://dx.doi.org/10.1007/978-3-030-32622-7_38DOI Listing
January 2020

Transcriptomics and Metabolomics in Amyotrophic Lateral Sclerosis.

Adv Exp Med Biol 2020 ;1195:205-212

National Center for Scientific Research "Demokritos", Institute of Nanoscience and Nanotechnology, Patriarchou Grigoriou & Neapoleos, Athens, Greece.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive and selective loss of motor neurons, muscle weakness, paralysis and death. The pathogenesis of ALS is not clearly understood, while reliable prognostic markers have not been identified to detect symptoms at earlier time points. The rapid development of microarray technology offers great potential for simultaneous analysis of the transcriptional expression of thousands of genes, aiming to determine novel candidate targets for efficient treatment. Read More

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http://dx.doi.org/10.1007/978-3-030-32633-3_29DOI Listing
January 2020

Amyotrophic Lateral Sclerosis: Current Status in Diagnostic Biomarkers.

Adv Exp Med Biol 2020 ;1195:179-187

Department of Informatics, Ionian University, Corfu, Greece.

Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disease that affects the human motor system. ALS is a highly heterogeneous disease, depending on several causative factors. The heterogeneity of the disease is also reflected in the variation of the symptoms in ALS patients. Read More

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http://dx.doi.org/10.1007/978-3-030-32633-3_26DOI Listing
January 2020

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases.

Int J Mol Sci 2020 May 25;21(10). Epub 2020 May 25.

Department of Neuroscience Rita Levi Montalcini, University of Turin, 10126 Turin, Italy.

Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease. However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. Read More

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http://dx.doi.org/10.3390/ijms21103719DOI Listing

Exploring the multimodal role of phytochemicals in the modulation of cellular signaling pathways to combat age-related neurodegeneration.

Sci Total Environ 2020 Jul 31;725:138313. Epub 2020 Mar 31.

Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11474, Saudi Arabia.

Neurodegeneration is the progressive loss of neuronal structures and functions that lead to copious disorders like Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS), and other less recurring diseases. Aging is the prime culprit for most neurodegenerative events. Moreover, the shared pathogenic factors of many neurodegenerative processes are inflammatory responses and oxidative stress (OS). Read More

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http://dx.doi.org/10.1016/j.scitotenv.2020.138313DOI Listing

Defining the Neural Kinome: Strategies and Opportunities for Small Molecule Drug Discovery to Target Neurodegenerative Diseases.

ACS Chem Neurosci 2020 May 28. Epub 2020 May 28.

Kinases are highly tractable drug targets that have reached unparalleled success in fields such as cancer but whose potential has not yet been realized in neuroscience. There are currently 55 approved small molecule kinase-targeting drugs, 48 of which have an anti-cancer indication. The intrinsic complexity linked to central nervous system (CNS) drug development and a lack of validated targets has hindered progress in developing kinase inhibitors for CNS disorders when compared to other therapeutic areas such as oncology. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00176DOI Listing

Lipids status and copper in a single rat astrocyte model for amyotrophic lateral sclerosis: correlative synchrotron-based X-ray and infrared imaging.

J Biophotonics 2020 May 28:e202000069. Epub 2020 May 28.

CELLS - ALBA Synchrotron, Barcelona, Spain.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, causing death of motor neurons controlling voluntary muscles. The pathological mechanisms of the disease are only partially understood. The hSOD1-G93A ALS rat model is characterized by an overexpression of human mutated SOD1, causing increased vulnerability by forming intracellular protein aggregates, inducing excitotoxicity, affecting oxidative balance, and disturbing axonal transport. Read More

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http://dx.doi.org/10.1002/jbio.202000069DOI Listing

Hand-onset weakness is a common feature of ALS patients with a NEK1 loss-of-function variant.

Ann Clin Transl Neurol 2020 May 27. Epub 2020 May 27.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: The NEK1 gene has been recently implicated in amyotrophic lateral sclerosis (ALS). This study aims to assess the influence of NEK1 variants on the occurrence of ALS and investigate the spectrum and clinical features of NEK1 loss-of-function (LOF) variants in a Taiwanese ALS cohort.

Methods: We screened 325 unrelated ALS patients for coding variants in NEK1 by targeted resequencing and queried the Taiwan Biobank database for NEK1 coding variants in 1000 Taiwanese healthy individuals. Read More

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http://dx.doi.org/10.1002/acn3.51064DOI Listing

Regulation of ALS-Associated SOD1 Mutant SUMOylation and Aggregation by SENP and PIAS Family Proteins.

J Mol Neurosci 2020 May 27. Epub 2020 May 27.

Department of Information and Communication Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo, 102-8554, Japan.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease specific to motor neurons. Pathogenic mutations in an ALS-associated gene encoding superoxide dismutase 1 (SOD1) have been identified in familial ALS (fALS) cases. SOD1 with fALS-linked mutations is prone to form cytotoxic aggregates that cause cellular dysfunction. Read More

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http://dx.doi.org/10.1007/s12031-020-01604-wDOI Listing

Sleep and Sleep Disruption in Amyotrophic Lateral Sclerosis.

Curr Neurol Neurosci Rep 2020 May 27;20(7):25. Epub 2020 May 27.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster (UKM), Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.

Purpose Of Review: In amyotrophic lateral sclerosis (ALS), sleep disruption is frequently present and substantially adds to disease burden. This review aims to summarize current knowledge on causes, pathophysiology, and treatment of sleep disturbances in ALS.

Recent Findings: Motor neuron degeneration and muscle weakness may lead to muscle cramps, pain, spasticity, immobilization, restless legs, sleep-disordered breathing, and difficulties to clear secretions. Read More

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http://dx.doi.org/10.1007/s11910-020-01047-1DOI Listing

Identification and verification of key genes in varicocele rats through high-throughput sequencing and bioinformatics analysis.

Andrologia 2020 May 27:e13662. Epub 2020 May 27.

Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.

Varicocele (VC) is the most common treatable cause of infertility, but it is difficult to distinguish fertile from infertile VC populations because the pathogenesis is unclear. In order to study the related mechanism of VC causing male sterility, we made VC rat model by surgery, analysed the rat epididymal spermatozoa and used the transcriptome sequencing to compare all the mRNA expression differences in testicular tissue between VC rats and control rats. The differentially expressed genes (DEGs) of testicular tissue were also screened by the limma package in R software (version 3. Read More

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http://dx.doi.org/10.1111/and.13662DOI Listing

The dichotomous role of the gut microbiome in exacerbating and ameliorating neurodegenerative disorders.

Expert Rev Neurother 2020 May 27. Epub 2020 May 27.

Department of Neurology, Mount Sinai School of Medicine , New York, NY 10029, USA.

Introduction: Age related neurodegenerative disorders affect millions of people around the world. The role of the gut microbiome (GM) in neurodegenerative disorders has been elucidated over the past few years. Dysbiosis of the gut microbiome ultimately results in neurodegeneration. Read More

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http://dx.doi.org/10.1080/14737175.2020.1775585DOI Listing

Characteristics and Therapeutic Potential of Dental Pulp Stem Cells on Neurodegenerative Diseases.

Front Neurosci 2020 7;14:407. Epub 2020 May 7.

Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan.

To evaluate the therapeutic potential of stem cells for neurodegenerative diseases, emphasis should be placed on clarifying the characteristics of the various types of stem cells. Among stem cells, dental pulp stem cells (DPSCs) are a cell population that is rich in cell proliferation and multipotency. It has been reported that transplantation of DPSCs has protective effects against models of neurodegenerative diseases. Read More

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http://dx.doi.org/10.3389/fnins.2020.00407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222959PMC

Fine tuning of the unfolded protein response by ISRIB improves neuronal survival in a model of amyotrophic lateral sclerosis.

Cell Death Dis 2020 May 26;11(5):397. Epub 2020 May 26.

Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008, Pamplona, Spain.

Loss of protein folding homeostasis features many of the most prevalent neurodegenerative disorders. As coping mechanism to folding stress within the endoplasmic reticulum (ER), the unfolded protein response (UPR) comprises a set of signaling mechanisms that initiate a gene expression program to restore proteostasis, or when stress is chronic or overwhelming promote neuronal death. This fate-defining capacity of the UPR has been proposed to play a key role in amyotrophic lateral sclerosis (ALS). Read More

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http://dx.doi.org/10.1038/s41419-020-2601-2DOI Listing

Mitigation of ALS pathology by neuron-specific inhibition of nuclear factor kappa B signaling.

J Neurosci 2020 May 26. Epub 2020 May 26.

CERVO Brain Research Centre, Québec, Québec, Canada;

To investigate the role of neuronal NF-κB activity in pathogenesis of amyotrophic lateral sclerosis (ALS), we generated transgenic mice with neuron-specific expression of a super-repressor form of the NF-κB inhibitor (IκBα-SR) which were then crossed with mice of both sexes, expressing ALS-linked gene mutants for TAR DNA-binding protein (TDP-43) and superoxide dismutase 1 (SOD1). Remarkably, neuronal expression of IκBα-SRtransgene in mice expressing TDP-43 or TDP-43 miceled to a decrease in cytoplasmic to nuclear ratio of human TDP-43. The mitigation of TDP-43 neuropathology by IκBα-SR, which is likely due toan induction of autophagy, was associated with amelioration of cognitive and motor deficits as well as reduction of motor neuron loss and gliosis. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.0536-20.2020DOI Listing

Emerging Drugs for the Treatment of Amyotrophic Lateral Sclerosis: A Focus on Recent Phase 2 Trials.

Expert Opin Emerg Drugs 2020 May 27:1-20. Epub 2020 May 27.

NEuroMuscular Omnicentre, Fondazione Serena Onlus , Milan, Italy.

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease involving both upper and lower motor neurons and resulting in increasing disability and death 3-5 years after onset of symptoms. Over 40 large clinical trials for ALS have been negative, except for Riluzole that offers a modest survival benefit, and Edaravone that modestly reduces disease progression in patients with specific characteristics. Thus, the discovery of efficient disease modifying therapy is an urgent need. Read More

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http://dx.doi.org/10.1080/14728214.2020.1769067DOI Listing

The Role of the Microbiota-Gut-Brain Axis and Antibiotics in ALS and Neurodegenerative Diseases.

Microorganisms 2020 May 23;8(5). Epub 2020 May 23.

Research Service, Louis Stokes Cleveland, Department of Veteran's Affairs Medical Center, Cleveland, OH 44106, USA.

The human gut hosts a wide and diverse ecosystem of microorganisms termed the microbiota, which line the walls of the digestive tract and colon where they co-metabolize digestible and indigestible food to contribute a plethora of biochemical compounds with diverse biological functions. The influence gut microbes have on neurological processes is largely yet unexplored. However, recent data regarding the so-called leaky gut, leaky brain syndrome suggests a potential link between the gut microbiota, inflammation and host co-metabolism that may affect neuropathology both locally and distally from sites where microorganisms are found. Read More

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http://dx.doi.org/10.3390/microorganisms8050784DOI Listing

ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS.

Int J Mol Sci 2020 May 21;21(10). Epub 2020 May 21.

Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motoneurons. To date, there is no effective treatment available. Exosomes are extracellular vesicles that play important roles in intercellular communication, recapitulating the effect of origin cells. Read More

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http://dx.doi.org/10.3390/ijms21103651DOI Listing

Genetics and Sex in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS): Is There a Link?

Int J Mol Sci 2020 May 21;21(10). Epub 2020 May 21.

Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no known cure. Approximately 90% of ALS cases are sporadic, although multiple genetic risk factors have been recently revealed also in sporadic ALS (SALS). The pathological expansion of a hexanucleotide repeat in ( is the most common genetic mutation identified in familial ALS, detected also in 5-10% of SALS patients. Read More

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http://dx.doi.org/10.3390/ijms21103647DOI Listing

Minimizing the Diagnostic Delay in Amyotrophic Lateral Sclerosis: The Role of Nonneurologist Practitioners.

Neurol Res Int 2020 11;2020:1473981. Epub 2020 May 11.

Department of Neurology, Nerve-Muscle Unit, CHU Bordeaux, Pellegrin Hospital, F-33096 Bordeaux, France.

Introduction: Amyotrophic lateral sclerosis (ALS), usually fatal in a few years, is a neurodegenerative disorder where the diagnostic delay, although variable according to the studies, remains too long. The main objective of this study was to determine the average time to diagnose ALS and the role of each physician, general practitioner (GP), or specialist (neurologist or not) involved in the management of these patients. The secondary objective was to propose some simple schemes to quickly identify an ALS suspicion with the aim to reduce this delay. Read More

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http://dx.doi.org/10.1155/2020/1473981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238340PMC