Synaptic defects associated with s-inclusion body myositis are prevented by copper.
Biometals
; 25(4): 815-24, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22573194
Sporadic-inclusion body myositis (s-IBM) is the most common skeletal muscle disorder to afflict the elderly, and is clinically characterized by skeletal muscle degeneration. Its progressive course leads to muscle weakness and wasting, resulting in severe disability. The exact pathogenesis of this disease is unknown and no effective treatment has yet been found. An intriguing aspect of s-IBM is that it shares several molecular abnormalities with Alzheimer's disease, including the accumulation of amyloid-ß-peptide (Aß). Both disorders affect homeostasis of the cytotoxic fragment Aß(1-42) during aging, but they are clinically distinct diseases. The use of animals that mimic some characteristics of a disease has become important in the search to elucidate the molecular mechanisms underlying the pathogenesis. With the aim of analyzing Aß-induced pathology and evaluating the consequences of modulating Aß aggregation, we used Caenorhabditis elegans that express the Aß human peptide in muscle cells as a model of s-IBM. Previous studies indicate that copper treatment increases the number and size of amyloid deposits in muscle cells, and is able to ameliorate the motility impairments in Aß transgenic C. elegans. Our recent studies show that neuromuscular synaptic transmission is defective in animals that express the Aß-peptide and suggest a specific defect at the nicotine acetylcholine receptors level. Biochemical analyses show that copper treatment increases the number of amyloid deposits but decreases Aß-oligomers. Copper treatment improves motility, synaptic structure and function. Our results suggest that Aß-oligomers are the toxic Aß species that trigger neuromuscular junction dysfunction.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Miosite de Corpos de Inclusão
/
Cobre
/
Junção Neuromuscular
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biometals
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Holanda