Résumé :
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Small stress proteins are characterized by a common alpha-crystallin domain. Among these proteins, Hsp27 and ?B-Crystallin are oligomeric molecular chaperones that are highly expressed in pathological conditions such as those generated by neuromuscular diseases. These proteins share the ability to protect cells against the toxicity mediated by aberrantly folded proteins or oxidative-inflammation conditions. In addition, they have anti-apoptotic properties. The missense mutation R120G in human ?B?Crystallin, which strongly decreases the chaperone activity of this protein, is associated in vivo with autosomal dominant myopathy, cardiomyopathy, and cataract (Vicart et al., 1998). In muscle cells, R120G mutant forms aggregates that contain desmin, the major chaperone substrate of ?B-Crystallin. Consequently, the structural organization of muscle cells is disorganized. Overexpression of Hsp27 or Hsp22 (an other small stress protein) results in the formation of complex oligomeric stuctures containing R120 mutant. As a consequence, the toxicity induced by R120G mutant is reduced, probably because of the partial refolding and restoration of the activity of this mutant. This implies that it may be possible to restore the function of R120G mutant by chaperone mimics that interfere with the aggregative process of this deleterious protein. Recent approaches using peptides aptamers that specifically target this protein support this assumption. Since the expression of small stress proteins has implications in pathologies as diverses as neurodegeneration, myopathies, asthma, cataracts and cancers, approaches towards therapeutic strategies will be discussed. Arrigo, A. P., Simon, S., Gibert, B., Kretz-Remy, C., Nivon, M., Czekalla, A., Guillet, D., Moulin, M., Diaz-Latoud, C., and Vicart, P. (2007). Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett. Vicart, P., Caron, A., Guicheney, P., Li, Z., Prevost, M. C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J. M., et al. crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20, 92-95.
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