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.

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

Pecorelli, Alessandra;CERVELLATI, Franco;STICOZZI, Claudia;VALACCHI, Giuseppe
Ultimo
2015

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.
2015
Pecorelli, Alessandra; Belmonte, Giuseppe; Meloni, Ilaria; Cervellati, Franco; Gardi, Concetta; Sticozzi, Claudia; De Felice, Claudio; Signorini, Cinz...espandi
File in questo prodotto:
File Dimensione Formato  
Pecorelli et al. FRBM 2015.pdf

solo gestori archivio

Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 10.51 MB
Formato Adobe PDF
10.51 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
nihms897383.AAM.pdf

accesso aperto

Tipologia: Post-print
Licenza: Creative commons
Dimensione 1.59 MB
Formato Adobe PDF
1.59 MB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2329662
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 18
social impact