Complexity of familial amyotrophic lateral sclerosis

Abstract

Each year approximately 400 patients are diagnosed with amyotrophic lateral sclerosis (ALS) in The Netherlands.Thesepatients are ~65 years of age at time of diagnosis.They develop progressive muscleweakness, frequently affecting their arms, legs and trunk, but also muscles involved in speech, swallowing and breathing. ALS patients usually die within three years due to respiratory failure. There is no cure for ALS and only Riluzole prolongs survival with two to three months. The pathogenesis of ALS is complex and involves both genetic and environmentalfactors. In ~5% of the cases more than one family member is affected. These patients are diagnosed with familial ALS (FALS). In the first part of this thesis, we will discuss eleven ALS-associated genes. The next part of this thesis will address other neurodegenerative diseases, including progressive muscular atrophy (PMA) and Parkinson’s disease (PD). Finally, we will describe several functional studies, investigating the effects of genetic abnormalities in ALS-associated genes.