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01.06.2009

PPAR-γ Agonist Azelaoyl PAF Increases Frataxin Protein and mRNA Expression. New Implications for the Friedreich’s Ataxia Therapy

verfasst von: Daniele Marmolino, Fabio Acquaviva, Michele Pinelli, Antonella Monticelli, Imma Castaldo, Alessandro Filla, Sergio Cocozza

Erschienen in: The Cerebellum | Ausgabe 2/2009

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Abstract

Friedreich’s ataxia is a neurodegenerative disease due to frataxin deficiency, and thus, drugs increasing the frataxin amount are excellent candidates for therapy. By screening Gene Expression Omnibus profiles, we identified records showing a frataxin response to the peroxisome proliferator-activated receptors gamma (PPAR-γ) agonist rosiglitazone. We decided to investigate the effect of the PPAR-γ agonist Azelaoyl PAF on the frataxin protein and mRNA expression profile. We treated human neuroblastoma cells SKNBE and primary fibroblasts from skin biopsies from Friedreich’s ataxia (FRDA) patients and healthy controls with the PPAR-γ agonist Azelaoyl PAF. We show in this paper for the first time that Azelaoyl PAF significantly increases the intracellular frataxin levels by twofold in the neuroblastoma cell line SKNBE and fibroblasts from FRDA patients and that Azelaoyl PAF increases frataxin protein through a transcriptional mechanism. PPAR-γ agonist Azelaoyl PAF increases both messenger RNA and protein levels of frataxin. We hypothesize that PPAR-γ agonists could play a role in the treatment of FRDA, and our results offer the logical bases to further investigate the usefulness of this group of agents for the treatment of the FRDA.

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Titel: PPAR-γ Agonist Azelaoyl PAF Increases Frataxin Protein and mRNA Expression. New Implications for the Friedreich’s Ataxia Therapy
verfasst von: Daniele Marmolino
Fabio Acquaviva
Michele Pinelli
Antonella Monticelli
Imma Castaldo
Alessandro Filla
Sergio Cocozza
Publikationsdatum: 01.06.2009
Verlag: Springer-Verlag
Erschienen in: The Cerebellum / Ausgabe 2/2009
Print ISSN: 1473-4222
Elektronische ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-008-0087-z

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