Pathogenesis of amyotrophic lateral sclerosis

Abstract

Introduction Amyotrophic lateral sclerosis (ALS) or motor neuron disease is a rapidly progressive neurodegenerative disorder. The primary involvement is of motor neurons in the brain, spinal cord and peripherally. There is secondary weakness of muscles and primary involvement of other brain regions, especially involving cognition. Sources of data Peer-reviewed journal articles and reviews. PubMed.gov Areas of agreement The pathogenesis of ALS remains largely unknown. There are a wide range of potential mechanisms related to neurodegeneration. An increasing number of genetic factors are recognized. Areas of controversy There remains controversy, or lack of knowledge, in explaining how cellular events manifest as the complex human disease. There is controversy as to how well cellular and animal models of disease relate to the human disease. Growing points Large-scale international collaborative genetic epidemiological studies are replacing local studies. Therapies related to pathogenesis remain elusive, with the greatest advances to date relating to provision of care (including multidisciplinary management) and supportive care (nutrition and respiratory support). Areas timely for developing research The identification of C9orf72 hexanucleotide repeats as the most frequent genetic background to ALS, and the association with frontotemporal dementia, gives the potential of a genetic background against which to study other risk factors, triggers and pathogenic mechanisms, and to develop potential therapies.