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.
Pecorelli, Alessandra; Belmonte, Giuseppe; Meloni, Ilaria; Cervellati, Franco; Gardi, Concetta; Sticozzi, Claudia; De Felice, Claudio; Signorini, Cinzia; Cortelazzo, Alessio; Leoncini, Silvia; Ciccoli, Lucia; Renieri, Alessandra; Jay Forman, Henry; Hayek, Joussef; Valacchi, Giuseppe
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2329662
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