Aggregation and proteasome: The case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy

Paola Rusmini, Daniela Sau, Valeria Crippa, Isabella Palazzolo, Francesca Simonini, Elisa Onesto, Luciano Martini, Angelo Poletti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1099-1111
Number of pages13
JournalNeurobiology of Aging
Volume28
Issue number7
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Atrophic Muscular Disorders
Proteasome Endopeptidase Complex
Testosterone
Motor Neuron Disease
Androgen Receptors
Motor Neurons
Ubiquitin
Neurodegenerative Diseases
Proteins
Ligands
polyglutamine

Keywords

  • Aggregation
  • Androgen receptor
  • Antiandrogen
  • Inclusion
  • Motor neuron diseases
  • Neurodegeneration
  • Polyglutamine diseases
  • Proteasome
  • Spinal and bulbar muscular atrophy
  • Testosterone

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Aggregation and proteasome : The case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy. / Rusmini, Paola; Sau, Daniela; Crippa, Valeria; Palazzolo, Isabella; Simonini, Francesca; Onesto, Elisa; Martini, Luciano; Poletti, Angelo.

In: Neurobiology of Aging, Vol. 28, No. 7, 07.2007, p. 1099-1111.

Research output: Contribution to journalArticle

Rusmini, P, Sau, D, Crippa, V, Palazzolo, I, Simonini, F, Onesto, E, Martini, L & Poletti, A 2007, 'Aggregation and proteasome: The case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy', Neurobiology of Aging, vol. 28, no. 7, pp. 1099-1111. https://doi.org/10.1016/j.neurobiolaging.2006.05.015
Rusmini, Paola ; Sau, Daniela ; Crippa, Valeria ; Palazzolo, Isabella ; Simonini, Francesca ; Onesto, Elisa ; Martini, Luciano ; Poletti, Angelo. / Aggregation and proteasome : The case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy. In: Neurobiology of Aging. 2007 ; Vol. 28, No. 7. pp. 1099-1111.
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