Rett (RTT) syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology.

Cholesterol metabolism is altered in Rett syndrome: A study on plasma and primary cultured fibroblasts derived from patients / Segatto, Marco; Trapani, Laura; Di Tunno, Ilenia; Sticozzi, Claudia; Valacchi, Giuseppe; Hayek, Joussef; Pallottini, Valentina. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 9:8(2014). [10.1371/journal.pone.0104834]

Cholesterol metabolism is altered in Rett syndrome: A study on plasma and primary cultured fibroblasts derived from patients

SEGATTO, MARCO;
2014

Abstract

Rett (RTT) syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology.
2014
Adolescent; Adult; Animals; Case-Control Studies; Cells, Cultured; Child; Child, Preschool; Cholesterol; Female; Fibroblasts; Humans; Hydroxymethylglutaryl CoA Reductases; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Knockout; Mutation; Proprotein Convertase 9; Proprotein Convertases; Receptors, LDL; Rett Syndrome; Scavenger Receptors, Class B; Serine Endopeptidases; Sterol Regulatory Element Binding Proteins; Young Adult; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
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Cholesterol metabolism is altered in Rett syndrome: A study on plasma and primary cultured fibroblasts derived from patients / Segatto, Marco; Trapani, Laura; Di Tunno, Ilenia; Sticozzi, Claudia; Valacchi, Giuseppe; Hayek, Joussef; Pallottini, Valentina. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 9:8(2014). [10.1371/journal.pone.0104834]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/974116
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