Cited by 23Genetics and Neurodevelopmental DisordersCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

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

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Pecorelli, Alessandra, Belmonte, Giuseppe, Meloni, Ilaria, Cervellati, Franco, Gardi, Concetta, Sticozzi, Claudia, De Felice, Claudio, Signorini, Cinzia +7 more·2015·Free Radical Biology and Medicine

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.

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Crossref · 10.1016/j.freeradbiomed.2015.05.010

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  1. [1]Rett A Uberein eigartiges hirnatrophisches Syndrom bei Hyperammoniamie in Kindesalter Wien Med Wochenschr 116 1966 723 728 5300597

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Authors
Pecorelli, A., Belmonte, G., Meloni, I., Cervellati, F., Gardi, C., Sticozzi, C., De Felice, C., Signorini, C., Cortelazzo, A., Leoncini, S., Ciccoli, L., Renieri, A., Jay Forman, H., Hayek, J., & Valacchi, G.
Affiliations
  • University of Siena (IT)
  • University of Ferrara (IT)
  • Ospedale Santa Maria alle Scotte (IT)
Corresponding author
Valacchi, Giuseppe
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2015-09
Volume
86
Pages
156-165
ISSN
0891-5849 (ISSN-L)
OpenAlex
W1589880975
Cited by
23
References
45
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 2
FWCI
1.60
Type
journal article
Language
en
Open access
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by-nc-nd)
  • Use Siena air (University of Siena) (submittedVersion)
Funders
  • Telethon Italy (GTB12001)
  • A.R. H.J.F (GGP11110A)
  • National Institutes of Health (ES020942)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
atypical Rett syndrome, scavenger receptor class B type I, Nrf2 activation, lipid profile, cholesterol homeostasis, oxidative stress, 4-hydroxynonenal, nitrotyrosine, protein adducts, ubiquitination, high-density lipoprotein receptor, MeCP2
MeSH terms
Epileptic Syndromes, Adolescent, Cells, Cultured, Child, Child, Preschool, Female, Fibroblasts, Humans, Lipids, Male, Spasms, Infantile, Rett Syndrome, Up-Regulation, Gene Expression, Protein Serine-Threonine Kinases, Oxidative Stress, Scavenger Receptors, Class B, NF-E2-Related Factor 2, Nitric Oxide Synthase Type II

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