Your browser doesn't support javascript.
loading
Proteostasis network alteration in lysosomal storage disorders: Insights from the mouse model of Krabbe disease.
Landi, Claudia; Luddi, Alice; Bianchi, Laura; Pannuzzo, Giovanna; Pavone, Valentina; Piomboni, Paola; Bini, Luca.
Afiliação
  • Landi C; Department of Life Sciences, University of Siena, Siena, Italy.
  • Luddi A; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
  • Bianchi L; Department of Life Sciences, University of Siena, Siena, Italy.
  • Pannuzzo G; Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania, Italy.
  • Pavone V; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
  • Piomboni P; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
  • Bini L; Department of Life Sciences, University of Siena, Siena, Italy.
J Neurosci Res ; 98(4): 718-733, 2020 04.
Article em En | MEDLINE | ID: mdl-31797419
In Krabbe disease, a mutation in GALC gene causes widespread demyelination determining cell death by apoptosis, mainly in oligodendrocytes and Schwann cells. Less is known on the molecular mechanisms induced by this deficiency. Here, we report an impairment in protein synthesis and degradation and in proteasomal clearance with a potential accumulation of the misfolded proteins and induction of the endoplasmic reticulum stress in the brain of 6-day-old twitcher mice (TM) (model of Krabbe disease). In particular, an imbalance of the immunoproteasome function was highlighted, useful for shaping adaptive immune response by neurological cells. Moreover, our data show an involvement of cytoskeleton remodeling in Krabbe pathogenesis, with a lamin meshwork disaggregation in twitcher oligodendrocytes in 6-day-old TM. This study provides interesting protein targets and mechanistic insight on the early onset of Krabbe disease that may be promising options to be tested in combination with currently available therapies to rescue Krabbe phenotype.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oligodendroglia / Doenças por Armazenamento dos Lisossomos / Proteostase / Leucodistrofia de Células Globoides Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oligodendroglia / Doenças por Armazenamento dos Lisossomos / Proteostase / Leucodistrofia de Células Globoides Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article