scholarly journals Impaired Autophagy in Motor Neurons: A Final Common Mechanism of Injury and Death

Physiology ◽  
2018 ◽  
Vol 33 (3) ◽  
pp. 211-224 ◽  
Author(s):  
Maria A. Gonzalez Porras ◽  
Gary C. Sieck ◽  
Carlos B. Mantilla
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Common Mechanism ◽  
Mechanism Of Injury ◽  
Therapeutic Approaches ◽  
Motor Neuron Diseases ◽  
Digestion Process ◽  
Cord Injury ◽  
Recent Developments ◽  
Health And Disease

Autophagy is a cellular digestion process that contributes to cellular homeostasis and adaptation by the elimination of proteins and damaged organelles. Evidence suggests that dysregulation of autophagy plays a role in neurodegenerative diseases, including motor neuron disorders. Herein, we review emerging evidence indicating the roles of autophagy in physiological motor neuron processes and its function in specific compartments. Moreover, we discuss the involvement of autophagy in the pathogenesis of motor neuron diseases, including spinal cord injury and aging, and recent developments that offer promising therapeutic approaches to mitigate effects of dysregulated autophagy in health and disease.

Motor Neuron Diseases

2014 ◽  
Author(s):  
Elena Ratti ◽  
Merit E. Cudkowicz ◽  
James D Berry
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Muscular Atrophy ◽  
Experimental Therapy ◽  
Rapid Progression ◽  
Motor Neuron Diseases ◽  
Efficacy Outcome ◽  
Single Disease Entity

The motor neuron diseases (MNDs) are a family of diseases commonly categorized by their propensity to affect upper or lower motor neurons and by their mode of inheritance. The chapter provides some content on infectious MNDs caused by viral infections affecting the motor neurons in the anterior horn of the spinal cord. However, the chapter devotes most of its attention to the inherited and sporadically occurring MNDs. The majority of research into adult MND focuses on amyotrophic lateral sclerosis (ALS) due to its high prevalence, rapid progression, and phenotypical similarities between its inherited form and its sporadic form. As our knowledge of genetic mechanisms underlying ALS pathology has grown, common themes have emerged. These include abnormalities in RNA biology, axonal transport, protein folding, and inflammatory responses. These themes currently drive much of the direction in ALS experimental therapy development. It is clear that MND is complex and involves several different molecular pathways. Given this complexity, ALS might not be a single disease entity, and if this is the case, treatment approaches may need to be targeted to specific pathologies rather than all ALS patients on a broad scale. Chapter content is enhanced by tables outlining the types of MNDs, criteria for supporting a diagnosis, first-line workup, the genes associated with ALS, ALS efficacy outcome measures, symptom management of ALS, and spinal muscular atrophy classification. Mechanisms of ALS are illustrated, and clinical photographs demonstrate symptoms. This chapter contains 252 references. 

Motor Neuron Diseases

2021 ◽  
pp. 752-759
Author(s):  
Eric J. Sorenson
Keyword(s):  
Motor Neuron ◽  
Incidence Rate ◽  
Motor Neurons ◽  
Anterior Horn Cell ◽  
Adult Onset ◽  
Motor Neuron Diseases ◽  
Kii Peninsula ◽  
Geographic Boundaries ◽  
Spinal Muscular Atrophies ◽  
Lateral Sclerosis

The motor neuron disorders are a clinically diverse group of diseases that share a pathologic loss of the motor neurons. The most common adult-onset disorder is amyotrophic lateral sclerosis (ALS). Other forms include the spinal muscular atrophies, infectious motor neuronopathies, and rare focal forms of anterior horn cell loss.Overall, the incidence rate of ALS is believed to be 1.5 to 2.0 cases per 100,000 person-years, and the prevalence rate is 4 to 6 cases per 100,000 population. Other than in sparsely populated geographic clusters (eg, Guam and the Kii Peninsula of Japan), the incidence rate seems consistent across ethnic and geographic boundaries.

scholarly journals A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS

2020 ◽  
Vol 10 (3) ◽  
pp. 58 ◽  
Author(s):  
Owen Connolly ◽  
Laura Le Gall ◽  
Gavin McCluskey ◽  
Colette G Donaghy ◽  
William J Duddy ◽  
...  
Keyword(s):  
Systematic Review ◽  
Amyotrophic Lateral Sclerosis ◽  
Respiratory Failure ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Disease Duration ◽  
Phenotype Correlation ◽  
Motor Neuron Diseases ◽  
Relationship Of ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.

Lower Motor Neuron Disease with Accumulation of Neurofilaments in a Cat

1976 ◽  
Vol 13 (6) ◽  
pp. 428-435 ◽  
Author(s):  
M. Vandevelde ◽  
C. E. Greene ◽  
E. J. Hoff
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Histological Examination ◽  
Muscle Atrophy ◽  
Motor Neurons ◽  
Nerve Cells ◽  
Lower Motor Neuron ◽  
Motor Neuron Diseases ◽  
Lower Motor Neuron Disease

A young cat had signs of tetraparesis that progressed to tetraplegia within a few weeks. Clinically, there was lower motor neuron disease with areflexia and muscle atrophy in all limbs. Degeneration of the motor neurons in the spinal cord was seen on histological examination. Ultrastructurally, the degeneration of nerve cells was characterized by abnormal proliferation of neurofilaments. These findings were compared to other motor neuron diseases and neurofibrillary accumulations in man and animals.

Retrograde transport and differential accumulation of serum proteins in motor neurons: Implications for motor neuron diseases

Neurology ◽  
1987 ◽  
Vol 37 (5) ◽  
pp. 843-843 ◽  
Author(s):  
T. Yamamoto ◽  
Y. Iwasaki ◽  
H. Konno ◽  
H. Iizuka ◽  
J.-X. Zhao
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Serum Proteins ◽  
Retrograde Transport ◽  
Motor Neuron Diseases

scholarly journals Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases

PLoS Genetics ◽  
2017 ◽  
Vol 13 (3) ◽  
pp. e1006680 ◽  
Author(s):  
Rachel A. Kline ◽  
Kevin A. Kaifer ◽  
Erkan Y. Osman ◽  
Francesco Carella ◽  
Ariana Tiberi ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Alpha Synuclein ◽  
Motor Neuron Diseases

scholarly journals Endovascular treatment of a basilar artery dissecting aneurysm

2007 ◽  
Vol 65 (4a) ◽  
pp. 1015-1017 ◽  
Author(s):  
Cassiano Mateus Forcelini ◽  
Francisco Tellechea Rotta ◽  
Naiana Posenato ◽  
Joana Stella Rovani ◽  
Paulo Sérgio Crusius ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Endovascular Treatment ◽  
Motor Neuron ◽  
Basilar Artery ◽  
Broad Spectrum ◽  
Dissecting Aneurysm ◽  
Therapeutic Approaches ◽  
Motor Neuron Diseases ◽  
Lateral Sclerosis

Fasciculations are symptoms present in a broad spectrum of conditions, ranging from normal manifestations to motor neuron diseases. They also represent the main picture of benign fasciculation syndrome. We report a case of such syndrome: a 48-years-old woman complaining about fasciculations for three decades who remained with the symptoms even after the compensation of a disclosed hyperthyroidism. The introduction of gabapentin rendered control of her fasciculations. The available data in the literature about the therapeutic approaches for fasciculations are revised, as long as the rare reports of evolution from patients with "benign" fasciculations to cases of amyotrophic lateral sclerosis, underlining the importance of following the patients with fasciculations.

scholarly journals An Inherited Lower Motor Neuron Disease of Pigs: Clinical Signs in Two Litters and Pathology of an Affected Pig

1994 ◽  
Vol 6 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Donal O'Toole ◽  
James Ingram ◽  
Val Welch ◽  
Katie Bardsley ◽  
Tom Haven ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Clinical Signs ◽  
Spinal Nerve ◽  
Neuronal System ◽  
Motor Neuron Diseases ◽  
System Degeneration ◽  
Progressive Neurodegeneration ◽  
Gross Lesions

A chronic progressive neurodegeneration, called hereditary porcine neuronal system degeneration (HPNSD), was recognized in a swine herd in Devon, England. Adult pigs that were presumed carriers of the dominantly inherited trait for HPNSD were transferred from England, where a breeding colony was maintained for 9 years, to the Wyoming State Veterinary Laboratory (WSVL) for study. Two litters of affected piglets were born to 2 carrier sows at the WSVL. Clinical signs of muscular tremors, paresis, or ataxia developed at 12–59 days of age in 4 of 6 liveborn pigs. Three other pigs were stillborn. In the 4 affected livebom pigs, clinical signs progressed and included symmetrical (3 pigs) or asymmetrical (1 pig) posterior paresis, bilateral knuckling of metatarsal-phalangeal or carpal joints, poor exercise tolerance, and in 1 pig, marked hind limb hypermetria. A 34-kg gilt exhibiting clinical signs of muscular tremors and posterior paresis and clinical signs for 22 days was euthanized and examined postmortem at 83 days of age. Apart from decubitus ulcers, gross lesions were absent. Microscopically, perikaryal vacuolation and osmiophilic lipid droplets were observed in atrophic alpha motor neurons in the spinal cord. There was axonal (Wallerian) degeneration in sulcomarginal and dorsal spinocerebellar tracts. Axonal degeneration also involved ventral but not dorsal spinal nerve roots, and was present in eight peripheral nerves sampled for histopathology. Changes in skeletal muscles were consistent with denervation atrophy and were most pronounced in M. tibialis cranialis of the 6 muscles sampled. Immunohistochemical staining of spinal cord for phosphorylated and nonphosphorylated neurofilaments did not reveal abnormal patterns, unlike some well-characterized inherited motor neuron diseases in other species.

scholarly journals With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3121
Author(s):  
Selin Altinok ◽  
Rebekah Sanchez-Hodge ◽  
Mariah Stewart ◽  
Kaitlan Smith ◽  
Jonathan C. Schisler
Keyword(s):  
Protein Quality ◽  
Cellular Stress Response ◽  
Therapeutic Approaches ◽  
Post Translational Modifications ◽  
Chaperone Function ◽  
Recent Developments ◽  
The Face ◽  
Health And Disease ◽  
Shock Proteins ◽  
Triage Decisions

Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintain protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensure cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, with a concentration on cardioprotection, neuroprotection, cancer, and autoimmune diseases. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.

scholarly journals A review: Management of motor neuron diseases

2022 ◽  
Vol 7 (4) ◽  
pp. 292-294
Author(s):  
Aarti Chopra ◽  
Ravi Kumar ◽  
Girendra Kumar Gautam
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Age At Onset ◽  
Motor Neuron Diseases ◽  
Progressive Degeneration ◽  
Review Management ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Motor neuron diseases are a group of chronic sporadic and hereditary neurological disorders characterized by progressive degeneration of motor neurons. These might affect the upper motor neurons, lower motor neurons, or both. The prognosis of the motor neuron disease depends upon the age at onset and the area of the central nervous system affected. Amyotrophic lateral sclerosis (ALS) has been documented to be fatal within three years of onset. This activity focuses on amyotrophic lateral sclerosis as the prototype of MND, which affects both the upper and the lower motor neurons and discusses the role of inter-professional team in the differential diagnosis, evaluation, treatment, and prognostication. It also discusses various other phenotypes of MND with an emphasis on their distinguishing features in requisite detail.

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