The unfolded protein response in familial amyotrophic lateral sclerosis

The unfolded protein response in familial amyotrophic lateral sclerosis.

Mutant superoxide dismutase type 1 (MTSOD1) is thought to cause ∼20% of cases of familial amyotrophic lateral sclerosis (FALS) because it misfolds and aggregates. Previous studies have shown that MTSOD1 accumulates inside the endoplasmic reticulum (ER) and activates the unfolded protein response (UPR), suggesting that ER stress is involved in the pathogenesis of FALS. We used a genetic approach...

Genetics of Familial Amyotrophic Lateral Sclerosis

Genetics of familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adultonset, rapidly progressive neurodegenerative disorder, caused by the selective loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Neuronal degeneration leads to weakness, muscular atrophy, and spasticity that evolve to paralysis. The typical age at onset is between 50 and 60 years, and the global incidence is 1...

Familial amyotrophic lateral sclerosis, a historical perspective

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease of the upper and lower motor neuron of unknown etiology. Although a familial cause for this disease has been suspected early one, it is only in the past two decades that advances in modern genetics led to the identification of more than 10 genes linked to familial ALS and helped us understand some of the complex genetic and envi...

Complexity of familial amyotrophic lateral sclerosis