Spinal and bulbar muscular atrophy (SBMA) is associated with an abnormal expansion of the (CAG)(n) repeat in the androgen receptor (AR) gene. Similar mutations have been reported in other proteins that cause neurodegenerative disorders. The CAG-coded elongated polyglutamine (polyGln) tracts induce the formation of neuronal intracellular aggregates. We have produced a model to study the effects of potentially 'neurotoxic' aggregates in SBMA using immortalized motoneuronal cells (NSC34) transfected with AR containing polyGln repeats of different sizes [(AR.Q (n = 0, 23 or 46)]. Using chimeras of AR.Q(n) and the green fluorescent protein (GFP), we have shown that aggregate formation occurs when the polyGln tract is elongated and AR is activated by androgens. In NSC34 cells co-expressing the AR with the polyGln of pathological length (AR.Q46) and the GFP we have noted the presence of several dystrophic neurites. Cell viability analyses have shown a reduced growth/survival rate in NSC34 expressing the AR.Q46, whereas testosterone treatment partially counteracted both cell death and the formation of dystrophic neurites. These observations indicate the lack of correlation between aggregate formation and cell survival, and suggest that neuronal degeneration in SBMA might be secondary to axonal/dendritic insults.

Motoneuronal cell death is not correlated with aggregate formation of androgen receptors containing an elongated polyglutamine tract / S. Simeoni, M.A. Mancini, D. Stenoien, M. Marcelli, N.L. Weigel, M. Zanisi, L. Martini, A. Poletti. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - 9:1(2000), pp. 133-144.

Motoneuronal cell death is not correlated with aggregate formation of androgen receptors containing an elongated polyglutamine tract

S. Simeoni
Primo
;
M. Zanisi;L. Martini
Penultimo
;
A. Poletti
Ultimo
2000

Abstract

Spinal and bulbar muscular atrophy (SBMA) is associated with an abnormal expansion of the (CAG)(n) repeat in the androgen receptor (AR) gene. Similar mutations have been reported in other proteins that cause neurodegenerative disorders. The CAG-coded elongated polyglutamine (polyGln) tracts induce the formation of neuronal intracellular aggregates. We have produced a model to study the effects of potentially 'neurotoxic' aggregates in SBMA using immortalized motoneuronal cells (NSC34) transfected with AR containing polyGln repeats of different sizes [(AR.Q (n = 0, 23 or 46)]. Using chimeras of AR.Q(n) and the green fluorescent protein (GFP), we have shown that aggregate formation occurs when the polyGln tract is elongated and AR is activated by androgens. In NSC34 cells co-expressing the AR with the polyGln of pathological length (AR.Q46) and the GFP we have noted the presence of several dystrophic neurites. Cell viability analyses have shown a reduced growth/survival rate in NSC34 expressing the AR.Q46, whereas testosterone treatment partially counteracted both cell death and the formation of dystrophic neurites. These observations indicate the lack of correlation between aggregate formation and cell survival, and suggest that neuronal degeneration in SBMA might be secondary to axonal/dendritic insults.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/153380
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