Anti-Excitotoxic and Antioxidant TGF-Beta Family Neurotrophic Factors: In Vitro Screening Models of Motor Neuron Degeneration

2002 ◽  
Author(s):  
Jeffrey D. Rothstein
Keyword(s):  
Motor Neuron ◽  
Neurotrophic Factors ◽  
In Vitro Screening ◽  
Tgf Beta ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration

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 Depletion of reduced glutathione enhances motor neuron degeneration in vitro and in vivo

Neuroscience ◽  
2007 ◽  
Vol 144 (3) ◽  
pp. 991-1003 ◽  
Author(s):  
L. Chi ◽  
Y. Ke ◽  
C. Luo ◽  
D. Gozal ◽  
R. Liu
Keyword(s):  
Motor Neuron ◽  
Reduced Glutathione ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration

scholarly journals A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Phaneendra Chennampally ◽  
Ambreen Sayed-Zahid ◽  
Prabakaran Soundararajan ◽  
Jocelyn Sharp ◽  
Gregory A. Cox ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Embryonic Stem ◽  
Immunosuppressive Drug ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Lateral Sclerosis

AbstractTAR DNA-binding protein-43 (TDP-43) is known to accumulate in ubiquitinated inclusions of amyotrophic lateral sclerosis affected motor neurons, resulting in motor neuron degeneration, loss of motor functions, and eventually death. Rapamycin, an mTOR inhibitor and a commonly used immunosuppressive drug, has been shown to increase the survivability of Amyotrophic Lateral Sclerosis (ALS) affected motor neurons. Here we present a transgenic, TDP-43-A315T, mouse model expressing an ALS phenotype and demonstrate the presence of ubiquitinated cytoplasmic TDP-43 aggregates with > 80% cell death by 28 days post differentiation in vitro. Embryonic stem cells from this mouse model were used to study the onset, progression, and therapeutic remediation of TDP-43 aggregates using a novel microfluidic rapamycin concentration gradient generator. Results using a microfluidic device show that ALS affected motor neuron survival can be increased by 40.44% in a rapamycin dosage range between 0.4-1.0 µM.

scholarly journals CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice

2021 ◽  
pp. 105538
Author(s):  
Valentina La Cognata ◽  
Elisabetta Golini ◽  
Rosario Iemmolo ◽  
Sara Balletta ◽  
Giovanna Morello ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Cortical Neurons ◽  
Neuromuscular Function ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Sod1g93a Mice

Motor neuron degeneration is attenuated in bax-deficient neurons in vitro

1999 ◽  
Vol 55 (5) ◽  
pp. 542-556 ◽  
Author(s):  
O. Bar-Peled ◽  
M. Knudson ◽  
S.J. Korsmeyer ◽  
J.D. Rothstein
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration

scholarly journals Limitations and Challenges in Modeling Diseases Involving Spinal Motor Neuron Degeneration in Vitro

2018 ◽  
Vol 12 ◽  
Author(s):  
Monica Bucchia ◽  
Samantha J. Merwin ◽  
Diane B. Re ◽  
Shingo Kariya
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Spinal Motor Neuron ◽  
Spinal Motor

Preclinical Testing of Neuroprotective Neurotrophic Factors in a Model of Chronic Motor Neuron Degeneration

1999 ◽  
Vol 6 (5) ◽  
pp. 335-346 ◽  
Author(s):  
Andrea M. Corse ◽  
Masako M. Bilak ◽  
Stephan R. Bilak ◽  
Mohamed Lehar ◽  
Jeffrey D. Rothstein ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Neurotrophic Factors ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Preclinical Testing

Histone Deacetylation and Motor Neuron Degeneration

2010 ◽  
Vol 9 (3) ◽  
pp. 279-284 ◽  
Author(s):  
S. Schmalbach ◽  
S. Petri
Keyword(s):  
Motor Neuron ◽  
Histone Deacetylation ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration

Cytoplasmic inclusions in spinal neurons of the motor neuron degeneration (Mnd) mouse

1993 ◽  
Vol 116 (1) ◽  
pp. 59-66 ◽  
Author(s):  
J.E. Mazurkiewicz ◽  
L.M. Callahan ◽  
M. Swash ◽  
J.E. Martin ◽  
A. Messer
Keyword(s):  
Motor Neuron ◽  
Spinal Neurons ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Cytoplasmic Inclusions
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