SOD1, the major constituent of the protein deposits in some familial and sporadic forms of ALS, propagates its misfolded conformation like prions, providing a plausible molecular basis for the focality and spreading of muscle weakness in ALS.
In agreement with the timing of CTE-SUMO1 accumulation, while onset of disease was not affected, the mutation caused an extension in progression time, a delay in the development of hindlimb and forelimb muscle weakness, and a significant increase in the lifespan of SOD1-G93A mice.
Importantly, these abnormalities in axonal excitability correlated with the motor amplitude (τSD: R = -0.38, P < .05 and TEd 90-100 milliseconds: R = -0.44, P < .01), muscle weakness (TEd 90-100 milliseconds: R = -0.32, P < .05), and the ALS Functional Rating Scale (TEd 90-100 milliseconds: R = -0.34, P < .05).
We report a heterozygous I113F mutation in a patient with familial ALS characterized by early and predominant bilateral vocal cord paralysis followed by descending spinal cord paresis.
Human familial amyotrophic lateral sclerosis with an H46R mutant Cu/Zn superoxide dismutase (SOD1) gene is characterized by initial muscle weakness and atrophy in the legs and a very long-term clinical course (approximately 15 years).
Expression of a mutant form of the human SOD1 gene in mice causes a degeneration of motor neurons, leading to progressive muscle weakness and hindlimb paralysis.
Expression of a mutant superoxide dismutase 1 (SOD1) gene in transgenic mice induces a gradual degeneration of cholinergic motor neurons in the spinal cord, causing progressive muscle weakness and hindlimb paralysis.