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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\u2010day\u2010old 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\u2010day\u2010old 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.<\/jats:p>","DOI":"10.1002\/jnr.24558","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T06:54:42Z","timestamp":1575442482000},"page":"718-733","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Proteostasis network alteration in lysosomal storage disorders: Insights from the mouse model of Krabbe disease"],"prefix":"10.1002","volume":"98","author":[{"given":"Claudia","family":"Landi","sequence":"first","affiliation":[{"name":"Department of Life Sciences University of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Luddi","sequence":"additional","affiliation":[{"name":"Department of Molecular and 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