Ubiquitin homeostasis disruption, a common cause of proteostasis collapse in amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis(ALS)is associated with proteostasis collapse:ALS is an unrelenting neurodegenerative disease that is characterized by the loss of motor neurons in the brain and spinal cord,resulting in the progressive atrophy,and eventual paralysis,of skeletal muscles.Death due to respiratory failure usually occurs within 2-5 years from symptom onset.Approximately 90%of ALS cases are of unknown etiology and are termed sporadic ALS(sALS).The remaining 10%of ALS cases present with a family history(familial ALS;fALS)and are associated with genetic mutations in a range of over 20 functionally heterogeneous genes.Regardless of disease origin,the pathological hallmark of ALS is the accumulation of ubiquitylated protein inclusions in motor neurons and surrounding glial cells.The presence of these inclusions,compromised largely of misfolded and aggregated proteins,implies a collapse in proteostasis.Proteostasis refers to the maintenance of the proteome in a state of balance or equilibrium so that a cell can perform its proper function.