Molecular basis of ALS and FTD: implications for translational studies / Molekularna osnova ALS-a i FTD-a: implikacije za translacijska istraživanja
| Autor: | Rajka M. Liscic |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Genetics
Pathology medicine.medical_specialty Mutation biology Tau protein Public Health Environmental and Occupational Health nutritional and metabolic diseases Neuropathology Arimoclomol Toxicology medicine.disease medicine.disease_cause TARDBP nervous system diseases chemistry.chemical_compound chemistry C9orf72 mental disorders biology.protein medicine Amyotrophic lateral sclerosis Frontotemporal dementia |
| Zdroj: | Archives of Industrial Hygiene and Toxicology. 66:285-290 |
| ISSN: | 0004-1254 |
| DOI: | 10.1515/aiht-2015-66-2679 |
| Popis: | Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The cause is unknown and no effective treatment currently exists. For ALS, there is only a drug Riluzole and a promising substance arimoclomol. The overlap between ALS and FTD occurs at clinical, genetic, and pathological levels. The majority of ALS cases are sporadic (SALS) and a subset of patients has an inherited form of the disease, familial ALS (FALS), with a common SOD1 mutation, also present in SALS. A few of the mutant genes identified in FALS have also been found in SALS. Recently, hexanucleotide repeat expansions in C9ORF72 gene were found to comprise the largest fraction of ALS- and FTD-causing mutations known to date. TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the pathological protein of FALS, SALS and, less frequently, FTD. The less frequent TDP-43 pathology in other forms of familial FTD has been linked to a range of mutations in GRN, FUS/TLS, rarely VCP, and other genes. TDP-43 and FUS/TLS have striking structural and functional similarities, most likely implicating altered RNA processing as a major event in ALS pathogenesis. The clinical overlap of the symptoms of FTD and ALS is complemented by overlapping neuropathology, with intracellular inclusions composed of microtubule-associated protein tau, TDP-43 and less frequently FUS, or unknown ubiquitinated proteins. Furthermore, new therapeutic approaches continue to emerge, by targeting SOD1, TDP-43 or GRN proteins. This review addresses new advances that are being made in our understanding of the molecular mechanisms of both diseases, which may eventually translate into new treatment options. |
| Databáze: | OpenAIRE |
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