Amyotrophic lateral sclerosis
- 1 October 2012
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Neurology
- Vol. 25 (5), 530-535
- https://doi.org/10.1097/wco.0b013e328356d328
Abstract
The field of amyotrophic lateral sclerosis (ALS) has seen a number of remarkable advances during recent years that will be summarized in this review. In particular, the progress in the molecular neuropathology with the discovery of pathogenic mutations in TAR DNA binding protein (TARDBP), fused in sarcoma (FUS), ubiquilin2 (UBQLN2) and most recently C9ORF72 (abbreviation for the open reading frame 72 on chromosome 9) has further substantiated the - clinically temporarily forgotten - relation of classic ALS to frontotemporal degeneration (FTD). Also, major progress has been made by the discovery of genes relevant for the disease, and pathogenetic concepts have been suggested which imply that not one, but multiple genetic and cell biological hits are involved in the causation of the disease. Progress in interventional therapies has remained poor; important recent examples are the failure of the interventional lithium and pioglitazone trials. However, a study of a third interventional compound - dexpramipexol - raises substantial hopes that the class of chemicals originally represented by riluzole - benzothiazoles - may provide additional therapeutic progress for ALS patients. Tremendous progress has been made in the field of ALS based on recent neuropathological and genetic discoveries. Moreover, the role of metabolism and nutrition in the pathogenesis of the disease is debated and may potentially serve as a future therapeutic target. For the facilitation and cost reduction of clinical trials, the development and international standardization of disease-specific 'wet' and 'dry' biomarkers is essential.Keywords
This publication has 54 references indexed in Scilit:
- A yeast functional screen predicts new candidate ALS disease genesProceedings of the National Academy of Sciences of the United States of America, 2011
- FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutationsBrain, 2011
- TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementiaThe Lancet Neurology, 2010
- Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALSNature, 2010
- A new subtype of frontotemporal lobar degeneration with FUS pathologyBrain, 2009
- Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral SclerosisScience, 2009
- Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6Science, 2009
- TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosisNature Genetics, 2008
- TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral SclerosisScience, 2008
- Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral SclerosisScience, 2006