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Beneficial effects of curcumin on GFAP filament organization and down-regulation of GFAP expression in an in vitro model of Alexander disease

Bachetti, Tiziana and Di Zanni, Eleonora and Balbi, Pietro and Ravazzolo, Roberto and Sechi, Gianpietro and Ceccherini, Isabella (2012) Beneficial effects of curcumin on GFAP filament organization and down-regulation of GFAP expression in an in vitro model of Alexander disease. Experimental Cell Research, Vol. 318 (15), p. 1844-1854. eISSN 1090-2422. Article.

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DOI: 10.1016/j.yexcr.2012.06.008

Abstract

Heterozygous mutations of the GFAP gene are responsible for Alexander disease, a neurodegenerative disorder characterized by intracytoplasmic Rosenthal fibers (RFs) in dystrophic astrocytes. In vivo and in vitro models have shown co-localization of mutant GFAP proteins with the small heat shock proteins (sHSPs) HSP27 and alphaB-crystallin, ubiquitin and proteasome components. Results reported by several recent studies agree on ascribing an altered cytoskeletal pattern to mutant GFAP proteins, an effect which induces mutant proteins accumulation, leading to impaired proteasome function and autophagy induction.
On the basis of the protective role shown by both these small heat shock proteins (sHSPs), and on the already well established neuroprotective effects of curcumin in several diseases, we have investigated the effects of this compound in an in vitro model of Alexander disease, consisting in U251-MG astrocytoma cells transiently transfected with a construct encoding for GFAP carrying the p.R239C mutation in frame with the reporter green fluorescent protein (GFP).
In particular, depending on the dose used, we have observed that curcumin is able to induce both HSP27 and alphaB-crystallin, to reduce expression of both RNA and protein of endogenous GFAP, to induce autophagy and, finally, to rescue the filamentous organization of the GFAP mutant protein, thus suggesting a role of this spice in counteracting the pathogenic effects of GFAP mutations.

Item Type:Article
ID Code:8702
Status:Published
Refereed:Yes
Uncontrolled Keywords:Alexander disease, curcumin, GFAP, autophagy, heat shock proteins
Subjects:Area 06 - Scienze mediche > MED/26 Neurologia
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:Academic Press / Elsevier
eISSN:1090-2422
Deposited On:26 Feb 2013 13:24

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