title: Activation of stress kinases in the brain of mucopolysaccharidosis IIIB mice.
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 with wild-type (Wt) littermates. Similarly, ERK1/2 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 with 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 with Wt animals, but no significant difference was found between the two p38MAPK analyzed in normal and affected neurons cultured in vitro. These data indicate the possible involvement of MAPK dysregulation in the early stage of MPS IIIB brain disease.
authors: Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.
authors: Francesca
authors: F
authors: Cecere
authors: Carmela
authors: C
authors: Di Domenico
authors: Daniele
authors: D
authors: Di Napoli
authors: Francesca
authors: F
authors: Boscia
authors: Paola
authors: P
authors: Di Natale
references: Am J Med Genet A. 2009 Jun;149A(6):1209-18
references: 19449420
references: Anal Biochem. 1993 May 1;210(2):282-91
references: 8512063
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: J Biol Chem. 1999 Mar 19;274(12):8029-38
references: 10075702
references: J Inherit Metab Dis. 2009 Apr;32(2):181-9
references: 19130290
references: Neuroreport. 1999 Aug 2;10(11):2411-5
references: 10439473
references: Neuroscience. 2003;119(2):387-97
references: 12770554
references: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1902-7
references: 12576554
references: J Neurosci. 2004 Nov 10;24(45):10229-39
references: 15537895
references: FASEB J. 1995 Jun;9(9):726-35
references: 7601337
references: J Neurosci Res. 2001 Jan 1;63(1):20-6
references: 11169610
references: PLoS One. 2008 May 28;3(5):e2296
references: 18509511
references: Mol Genet Metab. 2004 Aug;82(4):286-95
references: 15308126
references: J Neurochem. 2001 Jan;76(2):435-41
references: 11208906
references: Bioessays. 2003 Nov;25(11):1085-95
references: 14579249
references: Curr Alzheimer Res. 2005 Jan;2(1):3-18
references: 15977985
references: J Neuropathol Exp Neurol. 2006 Feb;65(2):142-51
references: 16462205
references: Proc Natl Acad Sci U S A. 2009 May 19;106(20):8332-7
references: 19416848
references: Mol Genet Metab. 2007 Apr;90(4):393-401
references: 17185018
references: J Cell Biol. 2004 May 10;165(3):357-69
references: 15123736
references: Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1775-89
references: 16987031
references: J Neurosci Res. 2002 Jul 1;69(1):30-8
references: 12111813
references: Mol Cell Neurosci. 2009 May;41(1):8-18
references: 19386237
references: Biochem J. 2005 Jun 1;388(Pt 2):639-46
references: 15649123
references: Acta Neuropathol. 2008 Oct;116(4):409-18
references: 18679696
references: Brain Res. 2009 Jul 7;1279:99-108
references: 19409882
references: J Appl Physiol (1985). 2004 Jan;96(1):203-10
references: 12959952
references: Oncogene. 2007 May 14;26(22):3279-90
references: 17496922
references: J Neurosci Res. 2009 Mar;87(4):978-90
references: 18951493
references: J Neurosci Res. 2007 Feb 15;85(3):612-22
references: 17139681
references: Brain Pathol. 2001 Apr;11(2):144-58
references: 11303790
references: Biochim Biophys Acta. 2010 Apr;1802(4):396-405
references: 20079433
references: Neuroscience. 2008 May 15;153(3):618-33
references: 18406062