AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsInformation ScienceHealth Care
Motor Neuron DiseaseMuscular Atrophy, SpinalMotor NeuronsNeuromuscular DiseasesSpinal Muscular Atrophies of ChildhoodBulbar Palsy, ProgressiveSurvival of Motor Neuron 1 ProteinSMN Complex ProteinsSpinal CordSurvival of Motor Neuron 2 ProteinAmyotrophic Lateral SclerosisMuscular AtrophyAtrophyNeuronsMuscular Disorders, AtrophicBulbo-Spinal Atrophy, X-LinkedAnterior Horn CellsNerve DegenerationNerve Tissue ProteinsSpinal Cord InjuriesAxonsSpinal Cord DiseasesSuperoxide DismutaseFasciculationNeuronal Apoptosis-Inhibitory ProteinDEAD Box Protein 20Cyclic AMP Response Element-Binding ProteinDisease Models, AnimalElectromyographyRNA-Binding ProteinsMotor CortexNeurons, AfferentMice, TransgenicNeurofilament ProteinsGaggingNeural ConductionTDP-43 ProteinopathiesInclusion BodiesFrontotemporal Lobar DegenerationFrontotemporal DementiaMotor ActivityMutationEvoked Potentials, MotorSpinal Nerve RootsBrainRNA-Binding Protein FUSToxascariasisMuscle, SkeletalNeuromuscular Junctionbeta-Hexosaminidase beta ChainRiluzoleUlnar NervePyrrolidonecarboxylic AcidPharyngostomyPick Disease of the BrainElectric InjuriesDeglutition DisordersPeripheral NervesBrain Injury, ChronicAction PotentialsLathyrismMuscle WeaknessPedigreeNeurologic ExaminationPhenotypeRibonucleoproteins, Small NuclearSandhoff DiseaseRats, TransgenicDementiaParalysisMarchiafava-Bignami DiseaseReceptors, AndrogenImmunohistochemistryMusclesAge of OnsetAxonal TransportElectric StimulationCricoid CartilageOptic AtrophyDNA Repeat ExpansionCells, CulturedTime FactorsMice, Inbred C57BLAnimals, Genetically ModifiedRecruitment, NeurophysiologicalSpinal NervesMagnetic Resonance ImagingExonsPathologyCoiled BodiesInjections, SpinalNervous System DiseasesGanglia, SpinalMice, KnockoutMutation, MissenseChromosomes, Human, Pair 5Disease ProgressionSynapsesSpastic Paraplegia, HereditaryNeurodegenerative Diseases
CordAmyotrophicDeath of motor neuronsLoss of motor neuronsDegenerationPhenotypeWeaknessAutosomal recessiveDisordersParalysisGeneProteinMiceTransgenicMutationsGenesSBMANeuronalIncluding muscular dystrophyNeuromuscular DiseasesDysfunctionSkeletalNeuropathiesBulbospinalDisorderCerebral cortexKugelberg-WelanderBulbar musculaturePathogenesisHumansDystrophiesSMN2TherapeuticFunctionalNervous systemHeterogeneousTransmit impulsesLower2021AbstractAnterior hornTherapeuticsInvolvementSynapsesDystrophy AssociationOnsetHereditary
Cord40
  • We performed exon-array analysis of RNA from SMN deficient mouse spinal cord at 3 time points, pre-symptomatic (P1), early symptomatic (P7), and late-symptomatic (P13). (ox.ac.uk)
  • Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is characterized by a progressive degeneration of spinal cord and cerebral cortex motor neurons, leading to muscular atrophy, paralysis, respiratory failure, and death. (rndsystems.com)
  • Researchers investigating VEGF-stimulated angiogenesis have found that homozygous vegf gene 'knock-in' (VEGF d/d ) mice, in which the hypoxia-response element of the promoter is disrupted, display reduced brain and spinal cord VEGF protein levels and develop unexpected symptoms that strongly resemble ALS. (rndsystems.com)
  • As a result of these developments, enthusiasm for the potential of VEGF as a therapeutic target Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is characterized by a progressive degeneration of spinal cord and cerebral cortex motor neurons, leading to muscular atrophy, paralysis, respiratory failure, and death. (rndsystems.com)
  • mice, in which the hypoxia-response element of the promoter is disrupted, display reduced brain and spinal cord VEGF protein levels and develop unexpected symptoms that strongly resemble ALS. (rndsystems.com)
  • EIAV lentiviral vector delivery of the human VEGF gene to the gastrocnemius muscle of an ALS-like SOD1 G93A -mutant mouse elicits stable expression of VEGF in the spinal cord, thereby preventing motor neuron death, delaying disease onset, reducing motor dysfunction, and increasing life expectancy. (rndsystems.com)
  • Administration of gene therapy viruses into skeletal muscle, where distal terminals of motor and sensory neurons reside, has been shown to result in extensive transduction of cells within the spinal cord, brainstem, and sensory ganglia. (frontiersin.org)
  • Crucially, some viral vectors (i.e., viruses specifically used to deliver genetic material into cells) have the potential to circumvent the blood-brain- (BBB) and blood-spinal cord barriers (BSCB) when intravenously injected. (frontiersin.org)
  • Spinal muscular atrophy (SMA) is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN) protein that affects alpha motoneurons in the spinal cord. (mdpi.com)
  • spinal muscular atrophy is an autosomal recessive disorder characterized by degeneration of alpha motor in anterior horn cells of brain and spinal cord, which results in muscular atrophy, hypotonia, fasciculations, areflexia, paralysis and even death in most severe cases. (annexpublishers.com)
  • ALS is a fatal neurodegenerative condition characterized by degeneration of upper and lower motor neuron in cerebral cor tex, cranial nerve nuclei and anterior horn cells of spinal cord. (annexpublishers.com)
  • Spinal muscular atrophy (SMA) is a serious neurodegenerative disorder caused by autosomal recessive mutations in the SMN (Survival Motor Neuron) gene and it is characterized by the death of motor neurons in spinal cord, the neurons that transfer the electrophysiological signals from the Central Nervous System to the muscles, controlling their movement, as a consequence of SMN protein reduction. (centrodinoferrari.com)
  • lumbar) MNs from brainstem and spinal cord of mice over-expressing the human SOD1 G93A (SOD1) mutation, in comparison to wild-type (WT) mice, at four postnatal (P) ages of 8-15, 28-35, 65-75, and 120 days. (frontiersin.org)
  • In SOD1 mice, dendritic changes occur at pre-symptomatic ages in both XII and spinal cord lumbar MNs. (frontiersin.org)
  • Prominent early changes in dendritic arbors and spines occur in susceptible cranial and spinal cord MNs, but are absent in MNs resistant to loss in ALS. (frontiersin.org)
  • Although these studies have provided insights into individual components of the neuro-motor network at specific time points in disease pathogenesis, there remains a need to define the onset and progression of neuronal pathology at successive stages of disease in ALS in key subcortical structures receiving cortical outputs: the striatum, hippocampus ( Spalloni and Longone, 2015 ), brainstem, and spinal cord. (frontiersin.org)
  • Nevertheless, we identified a small subset of genes that were alternatively spliced in the spinal cord compared with control mice before symptom onset, indicating a possible mechanistic role in disease. (ox.ac.uk)
  • Unexpectedly, for all stably-transmitting lines examined, MATR3 transgenic mRNA expression was more robust in muscle, with minimal expression in spinal cord. (biomedcentral.com)
  • Spinal muscular atrophies (SMAs) represent a rare group of inherited disorders that cause progressive degeneration of the anterior horn cells of the spinal cord. (medscape.com)
  • SMAs were first described in the 1890s, by Guido Werdnig, a physician from the University of Vienna, in his lecture "On a Case of Muscular Dystrophy with Positive Spinal Cord Findings. (medscape.com)
  • Both physicians conducted autopsies on their patients and found severe atrophy of the ventral roots of the spinal cord. (medscape.com)
  • Transverse myelitis is a neurological disorder caused by an inflammatory process of the grey and white matter of the spinal cord, and can cause axonal demyelination. (bionity.com)
  • The lesions are inflammatory , and involve the spinal cord on both sides. (bionity.com)
  • The lesions can be present anywhere in the spinal cord, though it is usually restricted to only a small portion. (bionity.com)
  • In some cases, the disease is presumedly caused by viral infections or vaccinations and has also been associated with spinal cord injuries, immune reactions, schistosomiasis and insufficient blood flow through spinal cord vessels. (bionity.com)
  • A major differentiation or distinction to be made is a similar condition due to compression of the spinal cord in the spinal canal, due to disease of the surrounding vertebral column. (bionity.com)
  • The symptoms and signs depend upon the level of the spinal cord involved and the extent of the involvement of the various long tracts. (bionity.com)
  • A lesion of the thoracic spinal cord (T1-12) will produce a spastic paraplegia. (bionity.com)
  • A lesion of the lower part of the spinal cord (L1-S5) often produces a combination of upper and lower motor neuron signs in the lower limbs. (bionity.com)
  • The degree and type of sensory loss will depend upon the extent of the involvement of the various sensory tracts, but there is often a "sensory level" (at the sensory segmental level of the spinal cord below which sensation to pin or light touch is impaired). (bionity.com)
  • The three main conditions to be considered in the differential diagnosis are: acute spinal cord trauma, acute compressive lesions of the spinal cord such as epidural metastatic tumour, and infarction of the spinal cord, usually due to insufficiency of the anterior spinal artery . (bionity.com)
  • The term "cerebral palsy" combines a group of syndromes resulting from underdevelopment or brain damage (often combined with spinal cord injury in the cervical spine) during the prenatal, intranatal and early postnatal periods. (doctorbersenev.ua)
  • Deep tendon (muscle stretch) reflex testing evaluates afferent nerves, synaptic connections within the spinal cord, motor nerves, and descending. (merckmanuals.com)
  • Motor neuron disease (MND) is a progressive neurodegenerative disorder primarily involving the motor neurons in the cerebral cortex, brain stem, and spinal cord [ 1 ]. (jneuropsychiatry.org)
  • Spinal cord injuries (SCIs) can have catastrophic effects on individuals resulting in loss of physical abilities and independence. (dovepress.com)
  • Spinal cord injury (SCI) can result in full or partial paralysis, which limits mobility-producing muscular activation. (dovepress.com)
  • An SCI results in a complex series of events that include a lesion within the spinal cord, glial scarring around the lesion, release of chemicals that inhibit axonal growth in the damaged area, and axonal demyelination of nearby but initially unaffected neurons. (dovepress.com)
  • The neurons involved (upper motor or corticospinal tract neurons) synapse with neurons in the spinal cord (lower motor neurons). (msdmanuals.com)
  • However, upper motor neuron dysfunction can decrease tone and reflexes if motor paralysis is sudden and severe (eg, in spinal cord transection, in which tone first decreases, then increases gradually over days to weeks) or if the lesion damages the motor cortex of the precentral gyrus and not nearby motor association areas. (msdmanuals.com)
  • Disorders of the spinal cord may affect tracts from upper motor neurons, lower motor neurons (anterior horn cells), or both. (msdmanuals.com)
Amyotrophic14
Death of motor neurons3
Loss of motor neurons3
Degeneration7
  • Further, degeneration of neuromuscular junctions, of synapses, and of axonal regions are features of SMA disease. (nih.gov)
  • However, the reason for selective motor neuron degeneration when SMN is reduced to levels which are tolerated by all other cell types is not currently understood. (ox.ac.uk)
  • KD is an inherited disorder characterized by degeneration of both motor and sensory neurons. (medscape.com)
  • Clinical diagnosis of exclusion based on progressive symptoms of upper and lower motor neuron degeneration in which no other explanation can be found. (wikipedia.org)
  • Our findings thus link the dysregulation of Chodl to the pathophysiology of motor neuron degeneration in SMA. (ox.ac.uk)
  • and corticobasal degeneration with FTDs because they share similar pathology and gene mutations affecting the tau protein. (merckmanuals.com)
  • Neurons in the brain of a patient with MND might undergo a process of degeneration. (jneuropsychiatry.org)
Phenotype7
  • Kennedy's disease or spinal bulbar muscular atrophy is a rare, inherited and slowly progressive multisystem disease mostly manifesting with a motor neuron disease phenotype leading to disability. (kennedysdisease.org)
  • As in vivo model we will use the SMA mouse model which harbours reduced SMN protein level and develops a phenotype resembling the human disease. (centrodinoferrari.com)
  • Dendritic structure and spine alterations correlate with the neuro-motor phenotype in ALS and with cognitive and extra-motor symptoms seen in patients. (frontiersin.org)
  • Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development. (cdc.gov)
  • 20 months were not overtly distinguishable from non-transgenic (NT) littermates based on basic motor phenotype. (biomedcentral.com)
  • Overall, our results indicate that increasing the levels of MATR3 in muscle can cause pathologic changes associated with myopathy, with MATR3 F115C expression causing overt muscle atrophy and a profound motor phenotype. (biomedcentral.com)
  • 2 In addition, the varied clinical presentations of MND also include (i) progressive muscle atrophy (PMA, ~ 10% of MND cases), a clinically pure lower motor neuron (LMN) phenotype, (ii) primary lateral sclerosis (PLS, 1-3% of MND cases), a clinically pure upper motor neuron (UMN) phenotype and (iii) progressive bulbar palsy (PBP, 1-2% of MND cases), an isolated bulbar phenotype with relative preservation of spinal motor neurons. (acnr.co.uk)
Weakness14
  • The serum level of creatinine starts to decrease before the onset of muscle weakness, followed by the emergence of hand tremor, a prodromal sign of the disease. (kennedysdisease.org)
  • Here, we tested this hypothesis using AR113Q knockin and human bacterial artificial chromosome/clone (BAC) transgenic mice that express the full-length polyQ-AR and display androgen-dependent weakness, muscle atrophy, and early death. (nih.gov)
  • The disease is characterised by a loss of motor neurones and resultant muscle weakness and inability to carry out co-ordinated motor tasks including breathing. (abdn.ac.uk)
  • This disease causes progressive weakness, muscle atrophy, deficiency in swallowing and difficulty in breathing mettere link alla pagina della SMA del centro dino ferrari). (centrodinoferrari.com)
  • Kugelberg-Welander (K-W) syndrome is a type of spinal muscular atrophy that causes weakness of the hip-girdle muscles. (amjcaserep.com)
  • Congenital Myasthenic Syndromes (CMSs) are rare inherited diseases of the neuromuscular junction characterized by muscle weakness. (istem.eu)
  • When a patient presents with nonspecific neurologic findings involving the extremities, with such symptoms as progressive weakness, abnormal fatigue, or muscle cramps, and clinical signs consistent with upper and lower motor neuron dysfunction, ALS should be considered in the differential diagnosis. (medscape.com)
  • Loss of these cells results in a progressive lower motor neuron disease that has no sensory involvement and that is manifested as hypotonia, weakness, and progressive paralysis. (medscape.com)
  • Soon after, Professor Johann Hoffmann from Heidelberg University presented a paper describing a syndrome of progressive atrophy, weakness, and death during the early childhood period of siblings with genetically normal parents. (medscape.com)
  • Symptoms include weakness and numbness of the limbs as well as motor, sensory, and sphincter deficits. (bionity.com)
  • 2 Lower motor neuron signs are clinically characterised by fasciculations, muscle wasting and weakness, while UMN signs include slowness of movement, increased tone, hyper-reflexia and extensor plantar responses. (acnr.co.uk)
  • Bulbar-onset disease may be evident in 20-25% of patients, characterised by progressive dysarthria, dysphagia, hoarseness, tongue wasting, weakness and fasciculations as well as emotional lability. (acnr.co.uk)
  • A 23 years old man was admitted to the hospital due to progressively developing four limbs weakness and possible atrophy for 2 years, dysarthria, choking and shortness of breath for 1 year. (jneuropsychiatry.org)
  • Peripheral polyneuropathies tend to be most noticeable in the longest nerves (ie, weakness is more prominent in the distal limb than the proximal and in legs more than arms) and produce signs of lower motor neuron dysfunction (eg, decreased reflexes and muscle tone). (msdmanuals.com)
Autosomal recessive4
  • Our efforts lead to the identification of novel molecular defects underlining several neurological disorders including Duchenne and Becker dystrophies, autosomal recessive and dominant muscular dystrophies, inner body myositis, disorders of glucose metabolism and storage, dysfunction of fatty acids metabolism and mitochondrial diseases. (centrodinoferrari.com)
  • Spinal muscular atrophy is an autosomal recessive neuromuscular disease caused by mutations in the multifunctional protein Survival of Motor Neuron, or SMN. (istem.eu)
  • Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by decreased levels of survival motor neuron protein (SMN). (bajajfinservhealth.in)
  • Pyruvate kinase deficiency is a hereditary disease with an autosomal recessive mode of inheritance, accompanied by hemolytic anemia. (mainecoon-russia.ru)
Disorders11
  • supporting a widespread putative molecular and therapeutic role in motor neuron disorders for this gene. (centrodinoferrari.com)
  • For a group of muscle-wasting disorders, see Motor neuron diseases . (wikipedia.org)
  • ALS is a motor neuron disease , which is a group of neurological disorders that selectively affect motor neurons , the cells that control voluntary muscles of the body. (wikipedia.org)
  • Scholar Rock is creating a pipeline of novel product candidates with the potential to transform the lives of patients suffering from a wide range of serious diseases, including neuromuscular disorders, cancer, and fibrosis. (businesswire.com)
  • Biogen looks forward to working with Alcyone to explore the potential of this device, which we believe will provide greater flexibility to people with spinal muscular atrophy and other neurological disorders as well as their doctors in making the right treatment decisions. (am-news.com)
  • There are many inherited and acquired clinical disorders caused by a defect in upper or lower motor neurone or the peripheral nerve. (musculoskeletalkey.com)
  • Motor neuron disease (MND) encompasses a group of rapidly progressive and universally fatal neurodegenerative disorders of the human motor system, first described in the mid-19th century by the French Neurologist Jean Martin Charcot. (acnr.co.uk)
  • Frontotemporal dementia (FTD) refers to sporadic and hereditary disorders that affect the frontal and temporal lobes, including Pick disease. (merckmanuals.com)
  • A wide variety of neurologic disorders may present with focal muscular atrophy (FMA). (medscape.com)
  • The organ ultimately affected is the muscle, although the pathology may be anywhere along the lower motor neuron (LMN) or, at times, secondary to nonneurologic disorders. (medscape.com)
  • and muscle disorders, such as muscular dystrophy or myositis. (lovinghandspodiatry.com)
Paralysis2
  • Because of the acuteness of this lesion, signs of spinal shock may be evident, in which the lower limbs will be flaccid and areflexic, rather than spastic and hyperreflexic as they should be in upper motor neuron paralysis. (bionity.com)
  • With the eradication of poliomyelitis, GBS is the most common cause of acute motor paralysis in children. (medscape.com)
Gene13
  • Comparative gene mapping among human, murine, and canine genomes have the potential to rapidly identify mutations that underlie various disease syndromes. (stanford.edu)
  • SMA is caused by mutations or deletions in a gene called survival motor neuron 1 ( SMN1 ). (nih.gov)
  • Researchers have identified at least one DCTN1 gene mutation that causes a nervous system disorder called distal hereditary motor neuronopathy type VIIB. (medlineplus.gov)
  • Spinal muscular atrophy is a severe motor neuron disease caused by inactivating mutations in the SMN1 gene leading to reduced levels of full-length functional SMN protein. (ox.ac.uk)
  • The disease is caused by a loss of functional copies of the SMN1 gene and its severity is, largely, inversely correlated to the number of copies of SMN2 . (biospace.com)
  • Virus-mediated gene therapy has the potential to deliver exogenous genetic material into specific cell types to promote survival and counteract disease. (frontiersin.org)
  • With thousands of clinical trials to date, gene therapy is a flourishing strategy with great promise for the treatment of diseases impacting the nervous system. (frontiersin.org)
  • The underlying cause of this disease is biallelic loss of survival motor neuron 1 (SMN1) gene. (annexpublishers.com)
  • Recently, our group performed a complex analysis of gene expression in induced pluripotent stem cell-derived motor neurons (iPSC) obtained with reprogramming of fibroblasts from SMA patients and healthy subjects. (centrodinoferrari.com)
  • Glycogen storage disease type III (GSDIII) is a rare inborn error of metabolism affecting liver, skeletal muscle, and heart due to mutations of the AGL gene encoding for the glycogen debranching enzyme (GDE). (istem.eu)
  • For example, molecular analysis of the survival motor neurone ( SMN ) gene identifies the majority of cases with SMA, and severity and prognosis are based on clinical features not muscle pathology. (musculoskeletalkey.com)
  • We'll also discuss Zolgensma, onasemnogene abeparvovec-xioi, a gene therapy that addresses the genetic root cause of the disease with a one-time dose, and its potentially transformative impact on babies and young children diagnosed with SMA. (reachmd.com)
  • SMA is caused by a lack of a functional survival motor neuron 1 also known as SMN1 gene. (reachmd.com)
Protein17
  • A primary research goal of the lab is to elucidate the function of Survival of Motor Neuron protein, SMN, which assembles a heptameric ring of Sm proteins on U snRNAs to form snRNPs that are essential components of the splicesome. (wikipedia.org)
  • Label-free quantitative proteomics on isolated synaptosomes from spinal cords of these animals identified 2030 protein groups. (nih.gov)
  • To carry out these roles, the complex's p150-glued subunit attaches (binds) to a protein called dynein, which acts as a motor, and also binds to a track-like system of small tubes called microtubules. (medlineplus.gov)
  • The altered protein may result in an abnormal dynactin complex and disturb interactions between the complex and microtubules, which would disrupt transport activities and impair the function of axons in neurons. (medlineplus.gov)
  • Over the past several years, hypotheses regarding the pathology of ALS have focused on oxidative damage, protein aggregation, neurofilament disorganization, and excitotoxicity. (rndsystems.com)
  • Spinal and bulbar muscular atrophy (SBMA) is caused by the polyglutamine androgen receptor (polyQ-AR), a protein expressed by both lower motor neurons and skeletal muscle. (nih.gov)
  • The genetic defect is well-characterised and attempts to replace or reduce the severe depletion of the key Survival of Motor Neurone (SMN) protein are ongoing. (abdn.ac.uk)
  • However, even when protein levels in motor neurones are increased and improvements in motor parameters are reported, survival is not increased. (abdn.ac.uk)
  • Li et al demonstrated nuclear inclusions in the spinal motor neurons of patients with KD that stained positively for androgen receptor protein when immunohistochemical methods are used. (medscape.com)
  • Spinal Muscular Atrophy (SMA) is a neurodegenerative, inherited disease caused by an insufficient amount of functional Survival of Motor Neurone protein (SMN), though the exact mechanism underlying this is not fully understood. (st-andrews.ac.uk)
  • CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, today announced two poster presentations as part of the World Muscle Society (WMS) Virtual Congress taking place September 20-24, 2021. (businesswire.com)
  • The underlying pathology of SMA is caused by insufficient production of the SMN (survival of motor neuron) protein, essential for the survival of motor neurons, and is encoded by two genes, SMN1 and SMN2. (businesswire.com)
  • Scholar Rock is a clinical-stage biopharmaceutical company focused on the discovery and development of innovative medicines for the treatment of serious diseases in which signaling by protein growth factors plays a fundamental role. (businesswire.com)
  • Spinal muscular atrophy (SMA) is characterized by the selective loss of spinal motor neurons owing to reduced levels of survival motor neuron (Smn) protein. (ox.ac.uk)
  • In addition to its well-established role in assembling constituents of the spliceosome, diverse cellular functions have been proposed for Smn, but the reason why low levels of this widely expressed protein result in selective motor neuron pathology is still debated. (ox.ac.uk)
  • We have examined in this study whether or not increased expression of clusterin is able to protect neuronal cells against intracellular protein aggregation and cytotoxicity, characteristics that are strongly implicated in a range of neurodegenerative diseases. (biomedcentral.com)
  • The ability of neurons to manage the burden of misfolded proteins and to resist their accumulation into insoluble protein deposits depends critically on the functioning of molecular chaperones. (biomedcentral.com)
Mice5
  • Moreover, USP7 knockdown suppressed disease phenotypes in SBMA and spinocerebellar ataxia type 3 (SCA3) fly models, and monoallelic knockout of Usp7 ameliorated several motor deficiencies in transgenic SBMA mice. (kennedysdisease.org)
  • We conclude that polyQ-AR expression in the periphery is an important contributor to pathology in SBMA mice and that peripheral administration of therapeutics should be explored for SBMA patients. (nih.gov)
  • Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice. (medscape.com)
  • To begin to understand how mutations in MATR3 may cause disease, here we provide initial characterization of transgenic (Tg) mice expressing human wild-type (WT) MATR3 (MATR3 WT ) and ALS-mutant F115C MATR3 (MATR3 F115C ) proteins under the control of the mouse prion promoter (MoPrP). (biomedcentral.com)
  • Electron microscope examination performed in ALS (the most common type of the MND) mice showed disorganized mitochondrial cristae and degenerating mitochondria in endothelial cells, astrocytes and motor neurons and extensive extracellular edema [ 6 ]. (jneuropsychiatry.org)
Transgenic1
  • We further showed that the expression of TDP-43 in transgenic Drosophila neurons induced ER stress and that co-expression of clusterin resulted in a dramatic clearance of mislocalized TDP-43 from motor neuron axons, partially rescued locomotor activity and significantly extended lifespan. (biomedcentral.com)
Mutations2
  • Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations. (medscape.com)
  • The findings suggest that analysis of muscle pathology in individuals harboring ALS-linked MATR3 mutations should be routinely considered. (biomedcentral.com)
Genes3
  • [6] [13] About half of these genetic cases are due to disease-causing variants in one of four specific genes . (wikipedia.org)
  • Here, we have performed functional studies of one of these genes, chondrolectin (Chodl), known to be highly expressed in motor neurons and important for correct motor axon outgrowth in zebrafish. (ox.ac.uk)
  • The non-specific lethal complex regulates genes and pathways genetically linked to Parkinson's disease. (medscape.com)
SBMA2
  • Split hand is not specific to ALS and can be caused by the peripheral mechanism alone in SBMA, whereas the effect of upper motor neuron lesion cannot be excluded in ALS. (kennedysdisease.org)
  • These observations suggest that the CIC-2 currents are affected in SBMA, an alteration that may contribute and potentially determine the pathophysiology of the disease. (kennedysdisease.org)
Neuronal6
  • increased nodal persistent sodium and reduced potassium currents that may accelerate motor neuronal death and differently affect axons-innervating different muscles. (kennedysdisease.org)
  • These pathways represent potential targets for therapy development with the goal of providing stability to the central synapses, thereby preserving neuronal integrity in the context of SMA disease. (nih.gov)
  • We are currently exploring the extent to which the non-neuronal pathologies described in animal models are also seen in human post-mortem material and are using cellular models to determine the vulnerabilities of SMA cells to hypoxic environments. (abdn.ac.uk)
  • As increased neuronal excitability correlates with structural changes in dendritic arbors and spines, we have examined longitudinal changes in dendritic structure in vulnerable neuron populations in a mouse model of familial ALS. (frontiersin.org)
  • Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. (ox.ac.uk)
  • Pick disease is a term used to describe pathologic changes in FTD, including severe atrophy, neuronal loss, gliosis, and presence of abnormal neurons (Pick cells) containing inclusions (Pick bodies). (merckmanuals.com)
Including muscular dystrophy1
Neuromuscular Diseases3
  • Retinopathies, genodermatoses, Limb-girdle muscular dystrophies, neuromuscular diseases & Myelinated fibers are part of our main scientific themes. (istem.eu)
  • The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases. (iospress.com)
  • Epidemiology of neuromuscular diseases, including the postpolio sequelae, in a Swedish county. (medscape.com)
Dysfunction8
  • Conclusion: In the general population without overt cardiac and liver disease, the presence of NAFLD was significantly associated with subclinical LV dysfunction, which may partly explain the elevated risk of HF in individuals with NAFLD. (bvsalud.org)
  • In longitudinal studies of exon-level changes in SMA mouse model tissues, designed to determine the contribution of splicing dysfunction to the disease, we have previously shown that a generalized defect in splicing is unlikely to play a causative role in SMA. (ox.ac.uk)
  • The MND is not only restricted to the motor system, but is a multisystem disorder involving extra-motor cortex areas, causing cognitive dysfunction and deficits in socioemotional and sensory processing pathways [ 3 ]. (jneuropsychiatry.org)
  • In the process of treating sensory neuropathy, our group has treated a subset of patients with foot drop (peroneal motor nerve dysfunction) which has also responded to the protocol. (lovinghandspodiatry.com)
  • Approximately six percent of our neuropathy patients present with common peroneal nerve motor dysfunction (foot drop). (lovinghandspodiatry.com)
  • Upper motor neuron dysfunction disinhibits lower motor neurons, resulting in increased muscle tone (spasticity) and increased muscle stretch reflexes (hyperreflexia). (msdmanuals.com)
  • ALS) may have findings of both upper and lower motor neuron dysfunction. (msdmanuals.com)
  • however, dysfunction of the inhibitory system via spinal interneurons may increase motor neuron excitability. (medscape.com)
Skeletal1
  • In the central nervous system, lower motor neurons are selectively affected, whereas pathology of patients and animal models also indicates involvement of skeletal muscle including loss of fasttwitch type 2 fibres and increased slow-twitch type 1 fibres, together with a glycolytic-to-oxidative metabolic switch. (kennedysdisease.org)
Neuropathies3
  • lower motor neurone) and inflammatory peripheral neuropathies. (musculoskeletalkey.com)
  • More commonly these distal symmetric neuropathies are sensory only, but this small percentage of patients also has motor involvement. (lovinghandspodiatry.com)
  • The CSF findings, in combination with certain clinical features, allowed AIDP to be distinguished from anterior horn cell diseases such as poliomyelitis, spinal muscular atrophy and from other neuropathies. (medscape.com)
Bulbospinal2
  • In 1982, Harding et al reclassified the disease as X-linked bulbospinal neuronopathy to reflect the sensory conduction abnormalities noted in several of their cases. (medscape.com)
  • Bulbospinal muscular atrophy (an X-linked disorder) involves only males. (medscape.com)
Disorder5
  • Spinal muscular atrophy (SMA) is a rare, and often fatal, genetic disorder that typically manifests in young children. (businesswire.com)
  • Changes in the muscle as a result of a denervating process are similar, irrespective of the site of the lesion, be it in the neurone or the peripheral nerve, and it is rarely possible to precisely define the disorder from a muscle biopsy, although certain patterns are suggestive. (musculoskeletalkey.com)
  • Progressive Supranuclear Palsy (PSP) Progressive supranuclear palsy is a rare, degenerative central nervous system disorder that progressively impairs voluntary eye movements and causes bradykinesia, muscular rigidity with progressive. (merckmanuals.com)
  • In the first instance, this defining feature of the neous disorder for which the aetiology, in the majority disease has been shown at post-mortem, as well as of cases, is unknown [1]. (lu.se)
  • The acute motor axonal neuropathy (AMAN) subtype of GBS is a purely motor disorder that is more prevalent amongst pediatric age groups. (medscape.com)
Cerebral cortex1
  • Alzheimer Disease Alzheimer disease causes progressive cognitive deterioration and is characterized by beta-amyloid deposits and neurofibrillary tangles in the cerebral cortex and subcortical gray matter. (merckmanuals.com)
Kugelberg-Welander1
  • Kugelberg Welander spinal muscular atrophy (also known as Wohlfart-Kugelberg-Welander syndrome or mild SMA) is a milder form of SMA, with symptoms typically presenting after age 18 months. (medscape.com)
Bulbar musculature1
Pathogenesis6
  • Animal models offer a unique opportunity to study the pathogenesis of neurologic diseases afflicting both humans and animals. (stanford.edu)
  • However, it remains unclear whether splicing abnormalities are present during early stages of the disease, which would be a requirement for a direct role in disease pathogenesis. (ox.ac.uk)
  • Although viewed as a motor neuronopathy, data from patients and mouse models suggest that muscle contributes to disease pathogenesis. (nih.gov)
  • We are confident that this project will have a significant impact on the neuroscience field by providing better knowledge on SMA disease pathogenesis, with the possibility of identifying new molecular targets complementary to the existing ones and of developing novel therapeutic approaches for SMA. (centrodinoferrari.com)
  • This review summarizes the physiological and pathological roles of alpha-synuclein and its implication in Parkinson's disease pathogenesis. (medscape.com)
  • This pathology has many behaviour options and various pathogenesis. (doctorbersenev.ua)
Humans1
  • Inherited diseases in dogs reliably replicate many hereditary diseases in humans. (stanford.edu)
Dystrophies1
  • Some neurogenic atrophies, however, may mimic some muscular dystrophies or myopathies, such as distal myopathies. (musculoskeletalkey.com)
SMN21
  • eIF4A3 FXR1 FXR2 Gemin2 (Previously known as SIP1) Gemin3/DDX20 Gemin4 Gemin5 Gemin6 Gemin7 hnRNPA1 RA33 hnRNPC PTBP1 hnRNPK hnRNPM hnRNPR hnRNPU hnRNPQ Y14 Magoh SMN1 SMN2 Spinal muscular atrophy Heterogeneous ribonucleoprotein particle Spliceosome Penn Medicine Announcement, [1], May 3, 2012 Chan, C. C. (wikipedia.org)
Therapeutic7
  • What is the function of the cells early in disease when therapeutic intervention would be most advantageous? (stanford.edu)
  • We conclude that future experiments developing therapeutic approaches specifically targeting neuromuscular synaptic vulnerability are likely to be required to prevent or delay disease onset and progression in human MND patients. (ox.ac.uk)
  • Spinal muscular atrophy (SMA) is a debilitating illness resulting from the deficient production of motor neurons in the central nervous system and can be fatal without timely therapeutic intervention. (biospace.com)
  • A better understanding of the molecular mechanisms underlying this complex pathology is needed to improve the therapeutic strategy. (centrodinoferrari.com)
  • In this workpackage, we will evaluate the therapeutic role of Stathmin 2 in in vitro SMA model assessing any modifications in disease markers in patient-derived cells after restoring Statmina2 expression. (centrodinoferrari.com)
  • This interaction has the potential to be key in SMA pathology and may have therapeutic potential. (st-andrews.ac.uk)
  • Focal atrophy of an individual muscle or group of muscles, often encountered clinically, may create diagnostic and therapeutic challenges. (medscape.com)
Functional4
  • We investigated the relationship between NAFLD and left ventricular (LV) functional remodelling in a general population sample without overt cardiac and liver disease. (bvsalud.org)
  • An additional exploratory analysis evaluating time to achieving various thresholds of improvement in Hammersmith Functional Motor Scale Expanded (HFMSE) scores further support the dose response in clinical efficacy. (businesswire.com)
  • A functional mini-GDE transgene corrects impairment in models of glycogen storage disease type III. (istem.eu)
  • 3. What is the substructure of the neuron (functional unit of the nervous system)? (fsu.edu)
Nervous system1
  • We can learn much by studying the temporal and spatial evolution of the lesions in the nervous system in spontaneously occurring or induced diseases in animals.The rapid development of the dog genome map brings an important benefit to the study of inherited canine diseases. (stanford.edu)
Heterogeneous1
  • We highlight important developments revealing the heterogeneous nature of vulnerability in populations of lower motor units in MND and examine how progress in our understanding of the molecular pathways underlying MND may provide insights into the regulation of synaptic vulnerability and pathology. (ox.ac.uk)
Transmit impulses1
Lower4
  • Muscles contain the synaptic connection between lower motor neurons and muscle fibers, i.e., the neuromuscular junction (NMJ), as well as specialized sensory nerve endings (e.g., muscle spindles). (frontiersin.org)
  • and one (8%) of ataluren on lower extremity and motor function. (iospress.com)
  • Lesions of the lower cervical (C2-T1) region will cause a combination of upper and lower motor neuron signs in the upper limbs, and exclusively upper motor neuron signs in the lower limbs. (bionity.com)
  • Clinically, ALS is characterised by co-existence of upper and lower motor neuron signs encompassing multiple body regions, with evidence of progressive deterioration. (acnr.co.uk)
20211
  • In continuation with the past Alzheimers 2021 Pulsus group proudly invites all the participants and sponsors across the world to participate within the 13th International conference on Dementia and Alzheimer Diseases (Alzheimers2021) which can be held during November 15, 2021 , as a Webinar . (pulsusconference.com)
Abstract1
  • Kennedy disease (KD) is named after William R. Kennedy, MD, who described this entity in an abstract in 1966. (medscape.com)
Anterior horn1
  • Although the most frequent cause is a (common) peroneal neuropathy at the neck of the fibula, other causes include anterior horn cell disease, lumbar plexopathies, L5 radiculopathy and partial sciatic neuropathy. (lovinghandspodiatry.com)
Therapeutics2
  • The Dreyfuss Lab is conducting research to understand the role of SMN in SMA pathology and using high throughput screening to discover potential therapeutics. (wikipedia.org)
  • Lumbar puncture (LP), commonly known as a spinal tap, is the current standard of care approach to delivering therapeutics into the CSF. (am-news.com)
Involvement1
  • [ 12 , 13 ] In contrast to prior studies suggesting upper motor neuron involvement in KD based on transcranial magnetic stimulation studies, one study found differences in cortical excitability between KD and ALS. (medscape.com)
Synapses1
  • Statistical data analysis revealed 65 specific alterations in the proteome of the central synapses at the early onset stage of disease. (nih.gov)
Dystrophy Association2
  • Fortunately, local ALS Association chapters and Muscular Dystrophy Association clinics , as well as the National ALS Registry , can provide some assistance. (medscape.com)
  • Our clinics have formal care center certifications from the Muscular Dystrophy Association, Parent Project Muscular Dystrophy, and CureSMA. (utah.edu)
Onset5
  • By evaluating the pathology and physiologic function or behavior in animals, we can begin to design rational interventional strategies to prevent, treat, or to delay the onset of neurodegenerative diseases. (stanford.edu)
  • Spine loss without dendritic changes was present in striatal neurons from disease onset. (frontiersin.org)
  • Hearing characteristics of infantile-onset Pompe disease after early enzyme-replacement therapy. (cdc.gov)
  • Severe backpain may occur in some patients at the onset of the disease. (bionity.com)
  • The majority of ALS patients present with limb-onset disease (65-75%), 10 spreading along the neuraxis to affect contiguous motor neurons. (acnr.co.uk)
Hereditary2
  • It is unclear how this mutation causes distal hereditary motor neuronopathy type VIIB. (medlineplus.gov)
  • [12] The remaining 5% to 10% of cases have a genetic cause, often linked to a history of the disease in the family , and these are known as familial ALS (hereditary). (wikipedia.org)