Synaptic defects associated with s-inclusion body myositis are prevented by copper
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-b-peptide (Ab). Both disorders affect homeostasis of the cytotoxic fragment Ab1-42 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 Abinduced pathology and evaluating the consequences of modulating Ab aggregation, we used Caenorhabditis elegans that express the Aβ 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 Ab transgenic C. elegans. Our recent studies show that neuromuscular synaptic transmission is defective in animals that express the Ab-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 Ab-oligomers. Copper treatment improves motility, synaptic structure and function. Our results suggest that Aboligomers are the toxic Ab species that trigger neuromuscular junction dysfunction. © 2012 Springer Science+Business Media, LLC.
|Título según WOS:||Synaptic defects associated with s-inclusion body myositis are prevented by copper|
|Título según SCOPUS:||Synaptic defects associated with s-inclusion body myositis are prevented by copper|
|Título de la Revista:||BIOMETALS|
|Fecha de publicación:||2012|
|Página de inicio:||815|
|Notas:||ISI, SCOPUS - ISI|