365 results match your criteria hallmark muscular


Neurodegeneration and axonal mRNA transportation.

Am J Neurodegener Dis 2021 15;10(1):1-12. Epub 2021 Feb 15.

Lincoln College, University of Oxford Oxford, UK.

The prevalence of neurodegenerative diseases is accelerating in rapidly aging global population. Novel and effective diagnostic and therapeutic methods are required to tackle the global issue of neurodegeneration in the future. A better understanding of the potential molecular mechanism causing neurodegeneration can shed light on dysfunctional processes in diseased neurons, which can pave the way to design and synthesize novel targets for early diagnosis during the asymptomatic phase of the disease. Read More

View Article and Full-Text PDF
February 2021

Implication of the NLRP3 Inflammasome in Bovine Age-Related Sarcopenia.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Veterinary Medicine and Animal Production, Unit of Pathology, University of Naples "Federico II", 80137 Naples, Italy.

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Read More

View Article and Full-Text PDF

Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion.

J Biol Chem 2021 Feb 18:100433. Epub 2021 Feb 18.

Centre for Organismal Studies (COS), Glycobiology, Heidelberg University, Heidelberg, Germany. Electronic address:

Defects in protein O-mannosylation lead to severe congenital muscular dystrophies collectively known as α-dystroglycanopathy. A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix. Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease. Read More

View Article and Full-Text PDF
February 2021

Dual proteotoxic stress accelerates liver injury via activation of p62-Nrf2.

J Pathol 2021 Feb 14. Epub 2021 Feb 14.

Department of Medicine III, University Hospital Aachen, Aachen, Germany.

Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. Read More

View Article and Full-Text PDF
February 2021

Effects of Survival Motor Neuron Protein on Germ Cell Development in Mouse and Human.

Int J Mol Sci 2021 Jan 11;22(2). Epub 2021 Jan 11.

Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan.

Survival motor neuron (SMN) is ubiquitously expressed in many cell types and its encoding gene, survival motor neuron 1 gene (SMN1), is highly conserved in various species. SMN is involved in the assembly of RNA spliceosomes, which are important for pre-mRNA splicing. A severe neurogenic disease, spinal muscular atrophy (SMA), is caused by the loss or mutation of SMN1 that specifically occurred in humans. Read More

View Article and Full-Text PDF
January 2021

HIP MUSCLE INHIBITION AFTER HIP ARTHROSCOPY: A ROLE FOR NEUROMUSCULAR ELECTRICAL STIMULATION.

Int J Sports Phys Ther 2020 Dec;15(6):1222-1228

Sparta Science, Menlo Park, CA, USA.

Background/purpose: The number of hip arthroscopies (HAs) performed in the United States is increasing exponentially. Previous authors have shown improvements in short- and mid-term functional outcomes after HA. Despite established overall improvements, functional and objective impairments may persist. Read More

View Article and Full-Text PDF
December 2020

Parallel All-Optical Assay to Study Use-Dependent Functioning of Voltage-Gated Ion Channels in a Miniaturized Format.

SLAS Discov 2021 Mar 17;26(3):460-469. Epub 2020 Dec 17.

AXXAM S.p.A, Bresso (Milan), Italy.

Voltage-gated ion channels produce rapid transmembrane currents responsible for action potential generation and propagation at the neuronal, muscular, and cardiac levels. They represent attractive clinical targets because their altered firing frequency is often the hallmark of pathological signaling leading to several neuromuscular disorders. Therefore, a method to study their functioning upon repeated triggers at different frequencies is desired to develop new drug molecules selectively targeting pathological phenotype. Read More

View Article and Full-Text PDF

Ferroptosis in Friedreich's Ataxia: A Metal-Induced Neurodegenerative Disease.

Biomolecules 2020 11 13;10(11). Epub 2020 Nov 13.

Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.

Ferroptosis is an iron-dependent form of regulated cell death, arising from the accumulation of lipid-based reactive oxygen species when glutathione-dependent repair systems are compromised. Lipid peroxidation, mitochondrial impairment and iron dyshomeostasis are the hallmark of ferroptosis, which is emerging as a crucial player in neurodegeneration. This review provides an analysis of the most recent advances in ferroptosis, with a special focus on Friedreich's Ataxia (FA), the most common autosomal recessive neurodegenerative disease, caused by reduced levels of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and antioxidant defenses. Read More

View Article and Full-Text PDF
November 2020

Early motor deficits in the phalangeal fine movements induced by chronic AMPA infusion in the rat spinal cord assessed by a novel method: Phalangeal tension recording test.

Neurosci Lett 2020 11 18;739:135411. Epub 2020 Oct 18.

División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Ciudad de México, Mexico. Electronic address:

Motor behavior alterations are a shared hallmark of neurodegenerative diseases affecting motor circuits, such as amyotrophic lateral sclerosis (ALS), Parkinson's, and Huntington's diseases. In patients and transgenic animal models of amyotrophic lateral sclerosis fine movements controlled by distal muscles are the first to be affected, but its study and knowledge remain poorly understood, mainly because most of the tests used for describing the motor alterations are focused on the function of proximal muscles and gross movements. In this study we demonstrate that alterations of phalangeal fine movements can be quantitatively evaluated using a novel procedure designed by us, phalangeal tension recording test, which showed high sensitivity to detect such alterations. Read More

View Article and Full-Text PDF
November 2020

Burst mitofusin activation reverses neuromuscular dysfunction in murine CMT2A.

Elife 2020 10 19;9. Epub 2020 Oct 19.

Department of Internal Medicine, Pharmacogenomics, Washington University School of Medicine, St Louis, United States.

Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal mutation. In mice expressing human T105M, intermittent mitofusin activation with a small molecule, MiM111, normalized CMT2A neuromuscular dysfunction, reversed pre-treatment axon and skeletal myocyte atrophy, and enhanced axon regrowth by increasing mitochondrial transport within peripheral axons and promoting in vivo mitochondrial localization to neuromuscular junctional synapses. Read More

View Article and Full-Text PDF
October 2020

Long non-coding RNAs in motor neuron development and disease.

J Neurochem 2021 Mar 10;156(6):777-801. Epub 2020 Oct 10.

Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.

Long non-coding RNAs (lncRNAs) are RNAs that exceed 200 nucleotides in length and that are not translated into proteins. Thousands of lncRNAs have been identified with functions in processes such as transcription and translation regulation, RNA processing, and RNA and protein sponging. LncRNAs show prominent expression in the nervous system and have been implicated in neural development, function and disease. Read More

View Article and Full-Text PDF

Andersen-Tawil Syndrome: A Comprehensive Review.

Cardiol Rev 2020 Sep 17. Epub 2020 Sep 17.

Scientific Director, Cardiovascular Division, Free University of Brussels (UZ Brussel) VUB, Brussels, Belgium.

Andersen-Tawil syndrome (ATS) is a very rare orphan genetic multisystem channelopathy without structural heart disease (with rare exceptions). ATS type 1 (ATS1) is inherited in an autosomal dominant fashion and is caused by mutations in the KCNJ2 gene, which encodes the α subunit of the K channel protein Kir2.1 (in ≈ 50 to 60% of cases). Read More

View Article and Full-Text PDF
September 2020

AAV9-DOK7 gene therapy reduces disease severity in Smn SMA model mice.

Biochem Biophys Res Commun 2020 09 30;530(1):107-114. Epub 2020 Jul 30.

Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, USA. Electronic address:

Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease caused by deletions or mutations in the survival motor neuron (SMN1) gene. An important hallmark of disease progression is the pathology of neuromuscular junctions (NMJs). Affected NMJs in the SMA context exhibit delayed maturation, impaired synaptic transmission, and loss of contact between motor neurons and skeletal muscle. Read More

View Article and Full-Text PDF
September 2020

Skeletal muscle regeneration in facioscapulohumeral muscular dystrophy is correlated with pathological severity.

Hum Mol Genet 2020 Sep;29(16):2746-2760

Randall Centre for Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant myopathy characterized by slowly progressive skeletal muscle weakness and wasting. While a regenerative response is often provoked in many muscular dystrophies, little is known about whether a regenerative response is regularly elicited in FSHD muscle, prompting this study. For comparison, we also examined the similarly slowly progressing myotonic dystrophy type 2 (DM2). Read More

View Article and Full-Text PDF
September 2020

Rodent Model of Muscular Atrophy for Sarcopenia Study.

J Bone Metab 2020 May 31;27(2):97-110. Epub 2020 May 31.

Department of Orthopaedic Surgery, Gyoengsang National University Hospital, Gyeongsang National University, Jinju, Korea.

The hallmark symptom of sarcopenia is the loss of muscle mass and strength without the loss of overall body weight. Sarcopenia patients are likely to have worse clinical outcomes and higher mortality than do healthy individuals. The sarcopenia population shows an annual increase of ~0. Read More

View Article and Full-Text PDF

Cell-Clearing Systems Bridging Repeat Expansion Proteotoxicity and Neuromuscular Junction Alterations in ALS and SBMA.

Int J Mol Sci 2020 Jun 4;21(11). Epub 2020 Jun 4.

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.

The coordinated activities of autophagy and the ubiquitin proteasome system (UPS) are key to preventing the aggregation and toxicity of misfold-prone proteins which manifest in a number of neurodegenerative disorders. These include proteins which are encoded by genes containing nucleotide repeat expansions. In the present review we focus on the overlapping role of autophagy and the UPS in repeat expansion proteotoxicity associated with chromosome 9 open reading frame 72 () and androgen receptor () genes, which are implicated in two motor neuron disorders, amyotrophic lateral sclerosis (ALS) and spinal-bulbar muscular atrophy (SBMA), respectively. Read More

View Article and Full-Text PDF

Networks in Posterior Cortex Epilepsies.

Authors:
Julia Jacobs

Neurosurg Clin N Am 2020 Jul 23;31(3):325-334. Epub 2020 Apr 23.

Alberta Children's Hospital, 28 Oki Drive Northwest, Calgary, Alberta T3B 6A8, Canada; Department of Pediatric Neurology and Muscular Disease, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Neuroscience, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Posterior cortex epilepsies comprise all epilepsies with seizures generated from the occipital, parietal, and posterior temporal areas. Seizures usually occur early in life. Visual phenomena during seizures are the hallmark for occipital lobe seizures. Read More

View Article and Full-Text PDF

Enhanced Clearance of Neurotoxic Misfolded Proteins by the Natural Compound Berberine and Its Derivatives.

Int J Mol Sci 2020 May 13;21(10). Epub 2020 May 13.

Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.

Background: Accumulation of misfolded proteins is a common hallmark of several neurodegenerative disorders (NDs) which results from a failure or an impairment of the protein quality control (PQC) system. The PQC system is composed by chaperones and the degradative systems (proteasome and autophagy). Mutant proteins that misfold are potentially neurotoxic, thus strategies aimed at preventing their aggregation or at enhancing their clearance are emerging as interesting therapeutic targets for NDs. Read More

View Article and Full-Text PDF

Motor transmission defects with sex differences in a new mouse model of mild spinal muscular atrophy.

EBioMedicine 2020 May 24;55:102750. Epub 2020 Apr 24.

Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada. Electronic address:

Background: Mouse models of mild spinal muscular atrophy (SMA) have been extremely challenging to generate. This paucity of model systems has limited our understanding of pathophysiological events in milder forms of the disease and of the effect of SMN depletion during aging.

Methods: A mild mouse model of SMA, termed Smn;SMN2, was generated by crossing Smn;SMN2 and Smn mice. Read More

View Article and Full-Text PDF

Facioscapulohumeral muscular dystrophy 1 patients participating in the UK FSHD registry can be subdivided into 4 patterns of self-reported symptoms.

Neuromuscul Disord 2020 04 12;30(4):315-328. Epub 2020 Mar 12.

John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Centre for Life, Newcastle NE1 3BZ, UK.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant incurable skeletal muscle disease. FSHD1 constitutes 95% of cases and is linked to truncation of the D4Z4 macrosatellite at 4q35. In most cases the condition initially presents with facial and proximal weakness of the upper limbs, but over the course of the disease involves lower limb and truncal muscles. Read More

View Article and Full-Text PDF

Epalrestat improves motor symptoms by reducing oxidative stress and inflammation in the reserpine induced mouse model of Parkinson's disease.

Animal Model Exp Med 2020 Mar 30;3(1):9-21. Epub 2019 Dec 30.

Laboratory of Pharmacology Department of Pharmaceutical Sciences School of Health & Life Sciences North South University Dhaka Bangladesh.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide. The current therapies for PD are symptom-based; they do not provide a cure but improve the quality of life. Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis. Read More

View Article and Full-Text PDF

MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease.

Acta Neuropathol 2020 07 18;140(1):63-80. Epub 2020 Apr 18.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Polyglutamine (polyQ) tract expansion leads to proteotoxic misfolding and drives a family of nine diseases. We study spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder of the neuromuscular system caused by the polyQ androgen receptor (AR). Using a knock-in mouse model of SBMA, AR113Q mice, we show that E3 ubiquitin ligases which are a hallmark of the canonical muscle atrophy machinery are not induced in AR113Q muscle. Read More

View Article and Full-Text PDF

Inhibition of Myostatin Reduces Collagen Deposition in a Mouse Model of Oculopharyngeal Muscular Dystrophy (OPMD) With Established Disease.

Front Physiol 2020 5;11:184. Epub 2020 Mar 5.

Department of Biological Sciences, Centre of Gene and Cell Therapy and Biomedical Sciences, Royal Holloway, University of London, Egham, United Kingdom.

Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease presented by ptosis, dysphagia, and limb weakness. Affected muscles display increased fibrosis and atrophy, with characteristic inclusion bodies in the nucleus. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to improve symptoms in models of muscular dystrophy. Read More

View Article and Full-Text PDF

Minocycline reduces experimental muscle hyperalgesia induced by repeated nerve growth factor injections in humans: A placebo-controlled double-blind drug-crossover study.

Eur J Pain 2020 07 13;24(6):1138-1150. Epub 2020 Apr 13.

School of Medicine, Western Sydney University, Penrith, NSW, Australia.

Background: Hyperalgesia is a heightened pain response to a noxious stimulus and is a hallmark of many common neuropathic and chronic pain conditions. In a double-blind placebo-controlled drug-crossover trial, the effects of concomitant and delayed minocycline treatment on the initiation and resolution of muscle hyperalgesia were tested.

Methods: An initial cohort (n = 10) received repeated injections (5 µg: days 0, 2 and 4) of nerve growth factor (NGF) in the flexor carpi ulnaris muscle of the forearm and pressure pain thresholds were collected at day 0 (control), day 7 (peak) and day 14 (recovery). Read More

View Article and Full-Text PDF

Small-molecule activation of lysosomal TRP channels ameliorates Duchenne muscular dystrophy in mouse models.

Sci Adv 2020 02 7;6(6):eaaz2736. Epub 2020 Feb 7.

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA.

Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca channel required for lysosomal exocytosis, produce a DMD-like phenotype. Read More

View Article and Full-Text PDF
February 2020

[Antisynthetase myopathy].

Authors:
Shigeaki Suzuki

Rinsho Shinkeigaku 2020 Mar 26;60(3):175-180. Epub 2020 Feb 26.

Department of Neurology, Keio University School of Medicine.

Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve skeletal muscle as well as many other organs. The classification of inflammatory myopathies has been based on clinical diagnoses, pathological diagnoses, and autoantibodies, independently. Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is a clinical entity based on the presence of aminoacyl transfer RNA synthetase (ARS) antibodies in patients' serum. Read More

View Article and Full-Text PDF

Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate.

JACC Basic Transl Sci 2019 Nov 2;4(7):778-791. Epub 2019 Oct 2.

Department of Neurology, University of Washington, Seattle, Washington.

Mutations in the gene encoding for dystrophin leads to structural and functional deterioration of cardiomyocytes and is a hallmark of cardiomyopathy in Duchenne muscular dystrophy (DMD) patients. Administration of recombinant adeno-associated viral vectors delivering microdystrophin or ribonucleotide reductase (RNR), under muscle-specific regulatory control, rescues both baseline and high workload-challenged hearts in an aged, DMD mouse model. However, only RNR treatments improved both systolic and diastolic function under those conditions. Read More

View Article and Full-Text PDF
November 2019

The 'mitochondrial contact site and cristae organising system' (MICOS) in health and human disease.

J Biochem 2020 Mar;167(3):243-255

Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, 23 Innovation Walk, Monash University, 3800 Melbourne, Victoria, Australia.

The 'mitochondrial contact site and cristae organising system' (MICOS) is an essential protein complex that promotes the formation, maintenance and stability of mitochondrial cristae. As such, loss of core MICOS components disrupts cristae structure and impairs mitochondrial function. Aberrant mitochondrial cristae morphology and diminished mitochondrial function is a pathological hallmark observed across many human diseases such as neurodegenerative conditions, obesity and diabetes mellitus, cardiomyopathy, and in muscular dystrophies and myopathies. Read More

View Article and Full-Text PDF

Homozygous missense variant in the TTN gene causing autosomal recessive limb-girdle muscular dystrophy type 10.

BMC Med Genet 2019 10 29;20(1):166. Epub 2019 Oct 29.

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

Background: Limb-girdle muscular dystrophies (LGMDs) are large group of heterogeneous genetic diseases, having a hallmark feature of muscle weakness. Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10. The phenotypic spectrum of titinopathies is expanding, as next generation sequencing (NGS) technology makes screening of this large gene possible. Read More

View Article and Full-Text PDF
October 2019

TGF-β Signaling in Cellular Senescence and Aging-Related Pathology.

Int J Mol Sci 2019 Oct 10;20(20). Epub 2019 Oct 10.

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Aging is broadly defined as the functional decline that occurs in all body systems. The accumulation of senescent cells is considered a hallmark of aging and thought to contribute to the aging pathologies. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates a myriad of cellular processes and has important roles in embryonic development, physiological tissue homeostasis, and various pathological conditions. Read More

View Article and Full-Text PDF
October 2019