Title of article :
Aggregation and proteasome: The case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy
Author/Authors :
Paola Rusmini، نويسنده , , Daniela Sau، نويسنده , , Valeria Crippa، نويسنده , , Isabella Palazzolo، نويسنده , , Francesca Simonini، نويسنده , , Elisa Onesto، نويسنده , , Luciano Martini، نويسنده , , Angelo Poletti، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2007
Pages :
13
From page :
1099
To page :
1111
Abstract :
Aggregates, a hallmark of most neurodegenerative diseases, may have different properties, and possibly different roles in neurodegeneration. We analysed ubiquitin-proteasome pathway functions during cytoplasmic aggregation in polyglutamine (polyQ) diseases, using a unique model of motor neuron disease, the SpinoBulbar Muscular Atrophy. The disease, which is linked to a polyQ tract elongation in the androgen receptor (ARpolyQ), has the interesting feature that ARpolyQ aggregation is triggered by the AR ligand, testosterone. Using immortalized motor neurons expressing ARpolyQ, we found that a proteasome reporter, YFPu, accumulated in absence of aggregates; testosterone treatment, which induced ARpolyQ aggregation, allowed the normal clearance of YFPu, suggesting that aggregation contributed to proteasome de-saturation, an effect not related to AR nuclear translocation. Using AR antagonists to modulate the kinetic of ARpolyQ aggregation, we demonstrated that aggregation, by removing the neurotoxic protein from the soluble compartment, protected the proteasome from an excess of misfolded protein to be processed.
Keywords :
Polyglutamine diseases , Spinal and bulbar muscular atrophy , testosterone , androgen receptor , Motor neuron diseases , Antiandrogen , aggregation , inclusion , Neurodegeneration , proteasome
Journal title :
Neurobiology of Aging
Serial Year :
2007
Journal title :
Neurobiology of Aging
Record number :
821023
Link To Document :
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