Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder
Open accessAbstract
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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Individuals with Rett syndrome and the related CDKL5 disorder have elevated lipid levels.
“Individuals with Rett syndrome and the related CDKL5 disorder have elevated lipid levels [42, 43].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [43]
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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
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 86
- Pages
- 156-165
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC5572621
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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