scholarly journals Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alizée Arnoux ◽  
Estelle Ayme-Dietrich ◽  
Stéphane Dieterle ◽  
Marc-Antoine Goy ◽  
Stephan Schann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Receptor Agonist ◽  
Receptor Expression ◽  
Disease Outcome ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Serotonin Neurons ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractDegeneration of brainstem serotonin neurons has been demonstrated in ALS patients and mouse models and was found responsible for the development of spasticity. Consistent with involvement of central serotonin pathways, 5-HT2B receptor (5-HT2BR) was upregulated in microglia of ALS mice. Its deletion worsened disease outcome in the Sod1G86R mouse model and led to microglial degeneration. In ALS patients, a polymorphism in HTR2B gene leading to higher receptor expression in CNS, was associated with increased survival in patients as well as prevention of microglial degeneration. Thus, the aim of our study was to determine the effect of a 5-HT2BR agonist : BW723C86 (BW), in the Sod1G86R mouse model. Despite good pharmacokinetic and pharmacological profiles, BW did not ameliorate disease outcome or motor neuron degeneration in a fast progressing mouse model of ALS despite evidence of modulation of microglial gene expression.

scholarly journals Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis

2018 ◽  
Vol 27 (21) ◽  
pp. 3761-3771 ◽  
Author(s):  
Owen M Peters ◽  
Elizabeth A Lewis ◽  
Jeannette M Osterloh ◽  
Alexandra Weiss ◽  
Johnny S Salameh ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Motor Neuron ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Sod1g93a Mouse ◽  
Lateral Sclerosis

Mapping of the motor neuron degeneration (Mnd) gene, a mouse model of amyotrophic lateral sclerosis (ALS)

Genomics ◽  
1992 ◽  
Vol 13 (3) ◽  
pp. 797-802 ◽  
Author(s):  
Anne Messer ◽  
Julie Plummer ◽  
Paul Maskin ◽  
John M. Coffin ◽  
Wayne N. Frankel
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Motor Neuron ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Lateral Sclerosis

scholarly journals The Links between ALS and NF-kB

2021 ◽  
Vol 22 (8) ◽  
pp. 3875
Author(s):  
Emma Källstig ◽  
Brian D. McCabe ◽  
Bernard L. Schneider
Keyword(s):  
Risk Factors ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Potential Role ◽  
Cell Types ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease wherein motor neuron degeneration leads to muscle weakness, progressive paralysis, and death within 3-5 years of diagnosis. Currently, the cause of ALS is unknown but, as with several neurodegenerative diseases, the potential role of neuroinflammation has become an increasingly popular hypothesis in ALS research. Indeed, upregulation of neuroinflammatory factors have been observed in both ALS patients and animal models. One such factor is the inflammatory inducer NF-kB. Besides its connection to inflammation, NF-kB activity can be linked to several genes associated to familial forms of ALS, and many of the environmental risk factors of the disease stimulate NF-kB activation. Collectively, this has led many to hypothesize that NF-kB proteins may play a role in ALS pathogenesis. In this review, we discuss the genetic and environmental connections between NF-kB and ALS, as well as how this pathway may affect different CNS cell types, and finally how this may lead to motor 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.

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