MAPK dysregulation in the brain pathology of mucopolysaccharidosis IIIB disease

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

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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.

Tipologia di documento:Tesi di dottorato
Parole chiave:Mucopolysaccharidosis; MAPK
Settori scientifico-disciplinari MIUR:Area 06 Scienze mediche > MED/03 GENETICA MEDICA
Area 05 Scienze biologiche > BIO/18 GENETICA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Nitsch, Lucionitsch@unina.it
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Di Natale, Paoladinatale@unina.it
Stato del full text:Accessibile
Data:29 Novembre 2010
Numero di pagine:95
Istituzione:Università degli studi di Napoli Federico II
Dipartimento o Struttura:Biologia e patologia cellullare e molecolare "L. Califano"
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Scuola di dottorato:Medicina molecolare
Denominazione del dottorato:Genetica e medicina molecolare
Ciclo di dottorato:23
Numero di sistema:8042
Depositato il:13 Dicembre 2010 23:29
Ultima modifica:29 Agosto 2012 12:21

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