Hereditary canine spinal muscular atrophy (HCSMA) is an autosomal dominant degenerative disorder of motor neurons. In homozygous animals, motor units produce decreased force output and fail during repetitive activity. Previous studies suggest that decreased efficacy of neuromuscular transmission underlies these abnormalities. To examine this, we recorded muscle fiber endplate currents (EPCs) an...

There is a desperate need for targeted therapeutic interventions that slow the progression of amyotrophic lateral sclerosis (ALS). ALS is a disorder with heterogeneous onset, which then leads to common final pathways involving multiple neuronal compartments that span both the central and peripheral nervous system. It is believed that excitotoxic mechanisms might play an important role in motor ...

Background: Spinal muscular atrophy (SMA) is a genetic motor neuron disease caused by mutations in the SMN1 (Survival Motor Neuron) gene, which leads to hypotonia, muscle weakness and respiratory involvement. Its most severe form, SMA type 1, starts before 6 months of life has high mortality due ventilatory failure. Nusinersen, first approved treatment for SMA, an antisense oligonucleotide intr...

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal motor neuron disorder. It results in progressive degeneration and death of upper and lower motor neurons, protein aggregation, severe muscle atrophy and respiratory insufficiency. Median survival with ALS is between 2 and 5 years from the onset of symptoms. ALS manifests as either familial ALS (FALS) (~10%...

Amyotrophic lateral sclerosis is a neurodegenerative disorder that results in the selective death of motor neurons in the central nervous system. This progressive motor neuron degeneration leads to death of the patient on average three to five years after onset of the disease. To date, no therapy is available. Many hypotheses have been formulated to explain the selective degeneration of motor n...

Activation of the transcription factor Nrf2 in astrocytes coordinates the upregulation of antioxidant defenses and confers protection to neighboring neurons. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. Non-neuronal cells, including astrocytes, shape m...

Mitochondria have been proposed as targets for toxicity in amyotrophic lateral sclerosis (ALS), a progressive, fatal adult-onset neurodegenerative disorder characterized by the selective loss of motor neurons. A decrease in the capacity of spinal cord mitochondria to buffer calcium (Ca 2 ) has been observed in mice expressing ALS-linked mutants of SOD1 that develop motor neuron disease with man...