Cecere, Francesca (2010) MAPK dysregulation in the brain pathology of mucopolysaccharidosis IIIB disease. [Tesi di dottorato] (Inedito)

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: MAPK dysregulation in the brain pathology of mucopolysaccharidosis IIIB disease
Autori:
AutoreEmail
Cecere, Francescacecerefrancesca18@libero.it
Data: 29 Novembre 2010
Numero di pagine: 95
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Biologia e patologia cellullare e molecolare "L. Califano"
Scuola di dottorato: Medicina molecolare
Dottorato: Genetica e medicina molecolare
Ciclo di dottorato: 23
Coordinatore del Corso di dottorato:
nomeemail
Nitsch, Lucionitsch@unina.it
Tutor:
nomeemail
Di Natale, Paoladinatale@unina.it
Data: 29 Novembre 2010
Numero di pagine: 95
Parole chiave: Mucopolysaccharidosis; MAPK
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/03 - Genetica medica
Area 05 - Scienze biologiche > BIO/18 - Genetica
Depositato il: 13 Dic 2010 22:29
Ultima modifica: 30 Apr 2014 19:44
URI: http://www.fedoa.unina.it/id/eprint/8042
DOI: 10.6092/UNINA/FEDOA/8042

Abstract

The accumulation of heparan sulfate (HS) in lysosomes is the primary consequence of the enzyme defect (α-N-acetylglucosaminidase) in Mucopolysaccharidosis type IIIB. This accumulation triggers a cascade of pathological events that progressively leads to CNS pathology. Here we examined the activation of the three major stress kinases in the neuronal tissue of a murine model of the disease. ERK1/2 was significantly higher in the cortex of 1-2-month-old affected animals compared to wild type (Wt) littermates. Similarly, ERK 1/2 was stimulated in neurons cultured from MPS IIIB mice. SAPK/JNK was also found to be activated in the cortex of 1-2-month-old affected animals compared to Wt subjects, and the same was found for cultured neurons. In contrast, the active form of p38MAPK was lower in the cortex of 1-month-old MPS IIIB mice compared to Wt animals, but no significant difference was found between the two p38MAPK analyzed in normal and affected neurons cultured in vitro. The differential activation of these kinases in the mouse brain at a very early stage of the disease course suggests a selective stress signature imposed by the lysosomal dysfunction.

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