Muscle-Derived GDNF: A Gene Therapeutic Approach for Preserving Motor Neuron Function in ALS

2015 ◽  
Author(s):  
Clive Svendsen ◽  
Genevieve Gowing
Keyword(s):  
Motor Neuron ◽  
Therapeutic Approach ◽  
Neuron Function

scholarly journals Omega-3 Hastens and Omega-6 Delays the Progression of Neuropathology in a Murine Model of Familial ALS

2017 ◽  
Vol 11 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Edward F. Boumil ◽  
Rishel Brenna Vohnoutka ◽  
Yuguan Liu ◽  
Sangmook Lee ◽  
Thomas B Shea
Keyword(s):  
Quality Of Life ◽  
Motor Neuron ◽  
Motor Function ◽  
Motor Neurons ◽  
Omega 3 ◽  
Self Medication ◽  
Familial Als ◽  
Neuron Function ◽  
The Impact

Background: Amyotrophic lateral sclerosis (ALS) is a progressive disease of motor neurons that has no cure or effective treatment. Any approach that could sustain minor motor function during terminal stages would improve quality of life. Objective: We examined the impact of omega-3 (Ω-3) and Ω-6, on motor neuron function in mice expressing mutant human superoxide dismutase-1 (SOD-1), which dominantly confers familial ALS and induces a similar sequence of motor neuron decline and eventual death when expressed in mice. Method: Mice received standard diets supplemented with equivalent amounts of Ω-3 and Ω-6 or a 10x increase in Ω-6 with no change in Ω-3 commencing at 4 weeks of age. Motor function and biochemical/histological parameters were assayed by standard methodologies. Results: Supplementation with equivalent Ω-3 and Ω-6 hastened motor neuron pathology and death, while 10x Ω-6 with no change in Ω-3 significantly delayed motor neuron pathology, including preservation of minor motor neuron function during the terminal stage. Conclusion: In the absence of a cure or treatment, affected individuals may resort to popular nutritional supplements such as Ω-3 as a form of “self-medication”. However, our findings and those of other laboratories indicate that such an approach could be harmful. Our findings suggest that a critical balance of Ω-6 and Ω-3 may temporarily preserve motor neuron function during the terminal stages of ALS, which could provide a substantial improvement in quality of life for affected individuals and their caregivers.

scholarly journals Assessing Rat Forelimb and Hindlimb Motor Unit Connectivity as Objective and Robust Biomarkers of Spinal Motor Neuron Function

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Markus E. Harrigan ◽  
Angela R. Filous ◽  
Andrew P. Tosolini ◽  
Renee Morris ◽  
Jan M. Schwab ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Unit ◽  
Compound Muscle Action Potential ◽  
Motor Units ◽  
Longitudinal Assessment ◽  
Muscle Contractility ◽  
Cross Sectional ◽  
Muscle Action Potential ◽  
Experimental Findings ◽  
Neuron Function

Abstract Sensitive and objective biomarkers of neuronal injury, degeneration, and regeneration can help facilitate translation of experimental findings into clinical testing. Whereas measures of upper motor neuron connectivity have been readily established, functional assessments of lower motor neuron (LMN) innervation of forelimb muscles are lacking. Compound muscle action potential (CMAP) and motor unit (MU) number estimation (MUNE) are well-established methods that allow longitudinal MU integrity monitoring in patients. In analogy we refined CMAP and MUNE methods for assessing spinal MU input in the rat forelimb and hindlimb. Repeated CMAP and MUNE recordings are robust (coefficients of variability: 4.5–11.3%), and MUNE measurements from forelimb wrist flexor muscles (415 ± 8 [SEM]) align with back-traced anatomical LMN counts (336 ± 16 [SEM]). For disease validation, cross-sectional blinded electrophysiological and muscle contractility measurements were obtained in a cohort of G93A SOD1 mutant overexpressing rats and compared with controls. Longitudinal assessment of mutant animals demonstrated progressive motor unit decline in the hindlimb to a greater extent than the forelimb. Hindlimb CMAP and MUNE demonstrated strong correlations with plantarflexion muscle contractility. Cross-species assessment of upper/fore- limb and lower/hind- limb motor units using objective electrophysiological CMAP and MUNE values as biomarkers will guide and improve bi-directional translation.

Mechanistic Insights of Astrocyte-Mediated Hyperactive Autophagy and Loss of Motor Neuron Function in SOD1L39R Linked Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 57 (10) ◽  
pp. 4117-4133
Author(s):  
Chetan Singh Rajpurohit ◽  
Vivek Kumar ◽  
Arquimedes Cheffer ◽  
Danyllo Oliveira ◽  
Henning Ulrich ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Neuron Function ◽  
Lateral Sclerosis

scholarly journals Progressive Loss of Motor Neuron Function in Wasted Mice: Effects of a Spontaneous Null Mutation in the Gene for the eEF1A2 Translation Factor

2005 ◽  
Vol 64 (4) ◽  
pp. 295-303 ◽  
Author(s):  
Helen J. Newbery ◽  
Thomas H. Gillingwater ◽  
Permphan Dharmasaroja ◽  
Josephine Peters ◽  
Stephen B. Wharton ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Null Mutation ◽  
Translation Factor ◽  
Progressive Loss ◽  
Neuron Function

scholarly journals Identification of Novel Compounds That Increase SMN Protein Levels Using an Improved SMN2 Reporter Cell Assay

2012 ◽  
Vol 17 (4) ◽  
pp. 481-495 ◽  
Author(s):  
Jonathan J. Cherry ◽  
Matthew C. Evans ◽  
Jake Ni ◽  
Gregory D. Cuny ◽  
Marcie A. Glicksman ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Neurodegenerative Disorder ◽  
Muscular Atrophy ◽  
Full Length ◽  
Reporter Cell ◽  
Protein Levels ◽  
Smn2 Gene ◽  
Smn Protein ◽  
Neuron Function ◽  
Survival Of Motor Neuron

Spinal muscular atrophy (SMA) is a neurodegenerative disorder that is characterized by progressive loss of motor neuron function. It is caused by the homozygous loss of the SMN1 ( survival of motor neuron 1) gene and a decrease in full-length SMN protein. SMN2 is a nearly identical homolog of SMN1 that, due to alternative splicing, expresses predominantly truncated SMN protein. SMN2 represents an enticing therapeutic target. Increasing expression of full-length SMN from the SMN2 gene might represent a treatment for SMA. We describe a newly designed cell-based reporter assay that faithfully and reproducibly measures full-length SMN expression from the SMN2 gene. This reporter can detect increases of SMN protein by an array of compounds previously shown to regulate SMN2 expression and by the overexpression of proteins that modulate SMN2 splicing. It also can be used to evaluate changes at both the transcriptional and splicing level. This assay can be a valuable tool for the identification of novel compounds that increase SMN2 protein levels and the optimization of compounds already known to modulate SMN2 expression. We present here preliminary data from a high-throughput screen using this assay to identify novel compounds that increase expression of SMN2.

Superconditioning TMS for examining upper motor neuron function in MND

2019 ◽  
Vol 237 (8) ◽  
pp. 2087-2103 ◽  
Author(s):  
Blair Calancie ◽  
Eufrosina Young ◽  
Mary Lou Watson ◽  
Dongliang Wang ◽  
Natalia Alexeeva
Keyword(s):  
Motor Neuron ◽  
Neuron Function
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