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Prion pathogenesis is unaltered in the absence of SIRPα-mediated "don't-eat-me" signaling.
Nuvolone, Mario; Paolucci, Marta; Sorce, Silvia; Kana, Veronika; Moos, Rita; Matozaki, Takashi; Aguzzi, Adriano.
Afiliación
  • Nuvolone M; Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Paolucci M; Amyloidosis Research and Treatment Center, Foundation Scientific Institute Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Pavia, Italy.
  • Sorce S; Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Kana V; Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Moos R; Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Matozaki T; Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Aguzzi A; Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
PLoS One ; 12(5): e0177876, 2017.
Article en En | MEDLINE | ID: mdl-28545141
Prion diseases are neurodegenerative conditions caused by misfolding of the prion protein, leading to conspicuous neuronal loss and intense microgliosis. Recent experimental evidence point towards a protective role of microglia against prion-induced neurodegeneration, possibly through elimination of prion-containing apoptotic bodies. The molecular mechanisms by which microglia recognize and eliminate apoptotic cells in the context of prion diseases are poorly defined. Here we investigated the possible involvement of signal regulatory protein α (SIRPα), a key modulator of host cell phagocytosis; SIRPα is encoded by the Sirpa gene that is genetically linked to the prion gene Prnp. We found that Sirpa transcripts are highly enriched in microglia cells within the brain. However, Sirpa mRNA levels were essentially unaltered during the course of experimental prion disease despite upregulation of other microglia-enriched transcripts. To study the involvement of SIRPα in prion pathogenesis in vivo, mice expressing a truncated SIRPα protein unable to inhibit phagocytosis were inoculated with rodent-adapted scrapie prions of the 22L strain. Homozygous and heterozygous Sirpa mutants and wild-type mice experienced similar incubation times after inoculation with either of two doses of 22L prions. Moreover, the extent of neuronal loss, microgliosis and abnormal prion protein accumulation was not significantly affected by Sirpa genotypes. Collectively, these data indicate that SIRPα-mediated phagocytosis is not a major determinant in prion disease pathogenesis. It will be important to search for additional candidates mediating prion phagocytosis, as this mechanism may represent an important target of antiprion therapies.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores Inmunológicos / Enfermedades por Prión / Microglía Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores Inmunológicos / Enfermedades por Prión / Microglía Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Suiza