ARTÍCULO

Identifying polyglutamine protein species in situ that best predict neurodegeneration

Autores: Miller, J.; Arrasate Iragui, Montserrat; Brooks, E.; Libeu, C. P.; Legleiter, J.; Hatters, D.; Curtis, J.; Cheung, K.; Krishnan, P.; Mitra, S.; Widjaja, K.; Shaby, B. A.; Lotz, G. P.; Newhouse, Y.; Mitchell, E. J.; Osmand, A.; Gray, M.; Thulasiramin, V.; Saudou, F.; Segal, M.; Yang, X. W.; Masliah, E.; Thompson, L. M.; Muchowski, P. J.; Weisgraber, K. H.; Finkbeiner, S.
Título de la revista: NATURE CHEMICAL BIOLOGY
ISSN: 1552-4450
Volumen: 7
Número: 12
Páginas: 925 - 934
Fecha de publicación: 2011
Lugar: WOS
Resumen:
Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal coping response to more toxic forms of polyQ. The exact structure of these more toxic forms is unknown. Here we show that the monoclonal antibody 3B5H10 recognizes a species of polyQ protein in situ that strongly predicts neuronal death. The epitope selectively appears among some of the many low-molecular-weight conformational states assumed by expanded polyQ and disappears in higher-molecular-weight aggregated forms, such as inclusion bodies. These results suggest that protein monomers and possibly small oligomers containing expanded polyQ stretches can adopt a conformation that is recognized by 3B5H10 and is toxic or closely related to a toxic species.