scholarly journals Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase

1998 ◽  
Vol 95 (16) ◽  
pp. 9626-9630 ◽  
Author(s):  
Sébastien Couillard-Després ◽  
Qinzhang Zhu ◽  
Philip C. Wong ◽  
Donald L. Price ◽  
Don W. Cleveland ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Transgenic Mice ◽  
Protective Effect ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Spinal Root ◽  
Old Mice ◽  
H Protein

To investigate the role of neurofilaments in motor neuron disease caused by superoxide dismutase (SOD1) mutations, transgenic mice expressing a amyotrophic lateral sclerosis-linked SOD1 mutant (SOD1G37R) were mated with transgenic mice expressing human neurofilament heavy (NF-H) subunits. Unexpectedly, expression of human NF-H transgenes increased by up to 65%, the mean lifespan of SOD1G37R mice. Microscopic examination corroborated the protective effect of NF-H protein against SOD1 toxicity. Although massive neurodegeneration occurred in 1-yr-old mice expressing SOD1G37R alone, spinal root axons and motor neurons were remarkably spared in doubly SOD1G37R;NF-H-transgenic littermates.

Mutations of Human Cu, Zn Superoxide Dismutase Expressed in Transgenic Mice Cause Motor Neuron Disease

1996 ◽  
pp. 113-122
Author(s):  
Mark E. Gurney ◽  
Arlene Y. Chiu ◽  
Mauro C. Dal Canto ◽  
John Q. Trojanowski ◽  
Virginia M.-Y. Lee
Keyword(s):  
Superoxide Dismutase ◽  
Transgenic Mice ◽  
Motor Neuron ◽  
Motor Neuron Disease

scholarly journals Overexpression of ferroptosis defense enzyme Gpx4 retards motor neuron disease of SOD1G93A mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liuji Chen ◽  
Ren Na ◽  
Kirsten Danae McLane ◽  
Cody Sylvester Thompson ◽  
Ju Gao ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Transgenic Mice ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Disease Onset ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Sporadic Als

AbstractDegeneration and death of motor neurons in Amyotrophic Lateral Sclerosis (ALS) are associated with increased lipid peroxidation. Lipid peroxidation is the driver of ferroptosis, an iron-dependent oxidative mode of cell death. However, the importance of ferroptosis in motor neuron degeneration of ALS remains unclear. Glutathione peroxidase 4 (Gpx4) is a key enzyme in suppressing ferroptosis by reducing phospholipid hydroperoxides in membranes. To assess the effect of increased protection against ferroptosis on motor neuron disease, we generated SOD1G93AGPX4 double transgenic mice by cross-breeding GPX4 transgenic mice with SOD1G93A mice, a widely used ALS mouse model. Compared with control SOD1G93A mice, both male and female SOD1G93AGPX4 mice had extended lifespans. SOD1G93AGPX4 mice also showed delayed disease onset and increased motor function, which were correlated with ameliorated spinal motor neuron degeneration and reduced lipid peroxidation. Moreover, cell toxicity induced by SOD1G93A was ameliorated by Gpx4 overexpression and by chemical inhibitors of ferroptosis in vitro. We further found that the anti-ferroptosis defense system in spinal cord tissues of symptomatic SOD1G93A mice and sporadic ALS patients might be compromised due to deficiency of Gpx4. Thus, our results suggest that ferroptosis plays a key role in motor neuron degeneration of ALS.

scholarly journals The critical role of membralin in postnatal motor neuron survival and disease

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Bo Yang ◽  
Mingliang Qu ◽  
Rengang Wang ◽  
Jon E Chatterton ◽  
Xiao-Bo Liu ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Early Onset ◽  
Critical Role ◽  
Mutant Mice ◽  
Neuron Survival ◽  
Motor Neuron Survival ◽  
Selective Death

Hitherto, membralin has been a protein of unknown function. Here, we show that membralin mutant mice manifest a severe and early-onset motor neuron disease in an autosomal recessive manner, dying by postnatal day 5–6. Selective death of lower motor neurons, including those innervating the limbs, intercostal muscles, and diaphragm, is predominantly responsible for this fatal phenotype. Neural expression of a membralin transgene completely rescues membralin mutant mice. Mechanistically, we show that membralin interacts with Erlin2, an endoplasmic reticulum (ER) membrane protein that is located in lipid rafts and known to be important in ER-associated protein degradation (ERAD). Accordingly, the degradation rate of ERAD substrates is attenuated in cells lacking membralin. Membralin mutations or deficiency in mouse models induces ER stress, rendering neurons more vulnerable to cell death. Our study reveals a critical role of membralin in motor neuron survival and suggests a novel mechanism for early-onset motor neuron disease.

scholarly journals Role of EphA4 in Mediating Motor Neuron Death in MND

2021 ◽  
Vol 22 (17) ◽  
pp. 9430
Author(s):  
Jing Zhao ◽  
Claire H. Stevens ◽  
Andrew W. Boyd ◽  
Lezanne Ooi ◽  
Perry F. Bartlett
Keyword(s):  
Cell Death ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Functional Outcomes ◽  
Underlying Mechanism ◽  
Neuron Death ◽  
Pathological Characteristics ◽  
Motor Neuron Death

Motor neuron disease (MND) comprises a group of fatal neurodegenerative diseases with no effective cure. As progressive motor neuron cell death is one of pathological characteristics of MND, molecules which protect these cells are attractive therapeutic targets. Accumulating evidence indicates that EphA4 activation is involved in MND pathogenesis, and inhibition of EphA4 improves functional outcomes. However, the underlying mechanism of EphA4’s function in MND is unclear. In this review, we first present results to demonstrate that EphA4 signalling acts directly on motor neurons to cause cell death. We then review the three most likely mechanisms underlying this effect.

scholarly journals ALS-Like Disorder in Three HIV-Positive Patients: Case Series

2021 ◽  
pp. 59-64
Author(s):  
Zachary Aaron Satin ◽  
Elham Bayat
Keyword(s):  
Antiretroviral Therapy ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Case Series ◽  
Retrospective Chart Review ◽  
Effective Control ◽  
Hiv Positive ◽  
Disease Course ◽  
Retroviral Infection

There appears to be a relationship between retroviruses such as HIV and the development of an ALS-like syndrome. Few cases have been reported; however, there exists evidence of a higher frequency of motor neuron disease in HIV-infected patients, as well as potential slowing and reversibility of disease course with combination antiretroviral therapy. We conducted a retrospective chart review of patients presenting to the George Washington University ALS Clinic from September 2006 to June 2018 to identify patients with HIV receiving HAART who were subsequently diagnosed with ALS or an ALS-like disorder. Our goals were to describe our patients’ disease course and compare them to general characteristics of ALS. We report three cases of HIV-positive individuals, all male, who were subsequently diagnosed with ALS. Each presented with symptoms of limb onset ALS with involvement of upper and lower motor neurons and whose disease originated at the cervical level. All three had been diagnosed with HIV prior to presentation and were presumably compliant with antiretroviral therapy throughout. Our patients demonstrated effective control of their HIV infection. Each experienced relatively slow progression of motor impairment compared to general ALS characteristics. Our study offers a distinct profile of HIV-positive patients compliant with HAART subsequently diagnosed with an ALS-like disorder. Further study should aim to uncover pathophysiological similarities between motor neuron disease both in the presence and absence of retroviral infection and to develop effective medical therapy for each.

scholarly journals Mutant Cu,Zn superoxide dismutase in motor neuron disease

AGE ◽  
1998 ◽  
Vol 21 (2) ◽  
pp. 85-89 ◽  
Author(s):  
Mark E. Gurney ◽  
Rugao Liu ◽  
John S. Althaus ◽  
Edward D. Hall ◽  
David A. Becker
Keyword(s):  
Superoxide Dismutase ◽  
Motor Neuron ◽  
Motor Neuron Disease

scholarly journals Amyotrophic lateral sclerosis: one or multiple causes?

2011 ◽  
Vol 3 (1) ◽  
pp. 4 ◽  
Author(s):  
Aline Furtado Bastos ◽  
Marco Orsini ◽  
Dionis Machado ◽  
Mariana Pimentel Mello ◽  
Sergio Nader ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Viral Infections ◽  
Vigorous Physical Activity ◽  
Disease Etiology ◽  
New Research ◽  
Lateral Sclerosis

The Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1), certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients.

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