Psychosine induces the dephosphorylation of neurofilaments by deregulation of PP1 and PP2A phosphatases.

ABSTRACT: Patients with Krabbe disease, a genetic demyelinating syndrome caused by deficiency of galactosyl-ceramidase and the resulting accumulation of galactosyl-sphingolipids, develop signs of a dying-back axonopathy compounded by a deficiency of large-caliber axons. Here, we show that axonal caliber in Twitcher mice, an animal model for Krabbe disease, is impaired in peripheral axons and is accompanied by a progressive reduction in the abundance and phosphorylation of the three neurofilament (NF) subunits. These changes correlate with an increase in the density of NFs per cross-sectional area in numerous mutant peripheral axons and abnormal increases in the activity of two serine/threonine phosphatases (PP1 and PP2A) in mutant tissue. Similarly, acutely isolated mutant cortical neurons show abno

SUBMITTER: Cantuti-Castelvetri L 

PROVIDER: S-EPMC3323754 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature