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Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder.

Abstract
CDKL5 mutation is associated with an atypical Rett syndrome (RTT) variant. Recently, cholesterol homeostasis perturbation and oxidative-mediated loss of the high-density lipoprotein receptor SRB1 in typical RTT have been suggested. Here, we demonstrate an altered lipid serum profile also in CDKL5 patients with decreased levels of SRB1 and impaired activation of the defensive system Nrf2. In addition, CDKL5 fibroblasts showed an increase in 4-hydroxy-2-nonenal- and nitrotyrosine-SRB1 adducts that lead to its ubiquitination and probable degradation. This study highlights a possible common denominator between two different RTT variants (MECP2 and CDKL5) and a possible common future therapeutic target.
AuthorsAlessandra Pecorelli, Giuseppe Belmonte, Ilaria Meloni, Franco Cervellati, Concetta Gardi, Claudia Sticozzi, Claudio De Felice, Cinzia Signorini, Alessio Cortelazzo, Silvia Leoncini, Lucia Ciccoli, Alessandra Renieri, Henry Jay Forman, Joussef Hayek, Giuseppe Valacchi
JournalFree radical biology & medicine (Free Radic Biol Med) Vol. 86 Pg. 156-65 (Sep 2015) ISSN: 1873-4596 [Electronic] United States
PMID26006105 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Lipids
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Protein Serine-Threonine Kinases
  • CDKL5 protein, human
Topics
  • Adolescent
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Epileptic Syndromes
  • Female
  • Fibroblasts (metabolism)
  • Gene Expression
  • Humans
  • Lipids (blood)
  • Male
  • NF-E2-Related Factor 2 (metabolism)
  • Nitric Oxide Synthase Type II (metabolism)
  • Oxidative Stress
  • Protein Serine-Threonine Kinases (genetics)
  • Rett Syndrome (blood, genetics)
  • Scavenger Receptors, Class B (genetics, metabolism)
  • Spasms, Infantile (blood, genetics)
  • Up-Regulation

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