Skeletal Muscle Metabolism: Origin or Prognostic Factor for Amyotrophic Lateral Sclerosis (ALS) Development?

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons, amyotrophy and skeletal muscle paralysis usually leading to death due to respiratory failure. While generally considered an intrinsic motor neuron disease, data obtained in recent years, including our own, suggest that motor neuron protection is not sufficient to counter the disease. The dismantling of the neuromuscular junction is closely linked to chronic energy deficit found throughout the body.

Sphingolipids metabolism alteration in the central nervous system: Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.

Sphingolipids are complex lipids. They play a structural role in neurons, but are also involved in regulating cellular communication, and neuronal differentiation and maturation. There is increasing evidence to suggest that dysregulated metabolism of sphingolipids is linked to neurodegenerative processes in amyotrophic lateral sclerosis (ALS), Parkinson's disease and Gaucher's disease.

Drug repositioning in neurodegeneration: An overview of the use of ambroxol in neurodegenerative diseases.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. While it is primarily characterized by the death of upper and lower motor neurons, there is a significant metabolic component involved in the progression of the disease. Two-thirds of ALS patients have metabolic alterations that are associated with the severity of symptoms.

Ambroxol Hydrochloride Improves Motor Functions and Extends Survival in a Mouse Model of Familial Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a multifactorial and fatal neurodegenerative disease. Growing evidence connects sphingolipid metabolism to the pathophysiology of ALS. In particular, levels of ceramides, glucosylceramides, and gangliosides are dysregulated in the central nervous system and at the neuromuscular junctions of both animal models and patients.

Sphingolipid Metabolism Is Dysregulated at Transcriptomic and Metabolic Levels in the Spinal Cord of an Animal Model of Amyotrophic Lateral Sclerosis.

Lipid metabolism is drastically dysregulated in amyotrophic lateral sclerosis and impacts prognosis of patients. Animal models recapitulate alterations in the energy metabolism, including hypermetabolism and severe loss of adipose tissue. To gain insight into the molecular mechanisms underlying disease progression in amyotrophic lateral sclerosis, we have performed RNA-sequencing and lipidomic profiling in spinal cord of symptomatic SOD1 mice.

Genetic analysis of CHCHD10 in French familial amyotrophic lateral sclerosis patients.

Mutations in CHCHD10 have been reported as the cause of a large panel of neurologic disorders. To confirm the contribution of this gene to amyotrophic lateral sclerosis (ALS) disease, we analyzed the 4 coding exons of CHCHD10 by Sanger sequencing in a cohort of 118 French familial ALS already excluded for all known ALS-related genes. We did not find any pathogenic mutation suggesting that CHCHD10 is not a major genetic cause of familial ALS, in France.