Autophagy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) is a neurodegenerative disease that primarily affects motor neurons. Mutations in multiple genes have been found to cause the familial forms of ALS. Research has been primarily focused on the familial ALS cases using animal and cellular models. The etiology of the disease is still not fully understood despite the intensive research. Increasing amount of evidence suggests that the perturbation or insufficiency of cellular protein turnover, especially autophagy, plays an important role in ALS pathogenesis. In this chapter, we review the involvement of impaired protein turnover by autophagy in ALS and discuss the role of familial ALS mutations in causing such autophagic impairment.