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191.
192.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
193.
Huet J Wyckmans J Wintjens R Boussard P Raussens V Vandenbussche G Ruysschaert JM Azarkan M Looze Y 《Cellular and molecular life sciences : CMLS》2006,63(24):3042-3054
Two chitinases, able to use tetra-N-acetylglucosamine, chitin and chitosan as substrates, were characterized after purification from Carica papaya latex. The complete amino acid sequence of the major form and about 40% of the minor one were determined through proteolytic
digestions and mass spectroscopy analysis. Sequencing demonstrated that both papaya chitinases are members of the family 19
of glycosyl hydrolases (GH19). Based on the known 3-D structures of other members of family GH19, it was expected that papaya
chitinases would adopt all-alpha structures. However, circular dichroism and infrared spectroscopy indicated, for the papaya
chitinases, a content of 15–20% of extended structures besides the expected 40% of alpha helices. Since the fully sequenced
papaya chitinase contains a large number of proline residues the possibility that papaya chitinase contains polyproline II
stretches was examined in the context of their resistance against proteolytic degradation.
Received 11 July 2006; received after revision 13 October 2006; accepted 25 October 2006 相似文献
194.
The Wnt/beta-catenin/TCF4 pathway plays critical roles in the maintenance of small intestinal epithelium; however, downstream
targets of the beta-catenin/TCF4 complex are not extensively characterized. We identified miR-30e as an immediate target activated
by the beta-catenin/TCF4 complex. miR-30e was detected in the peri-nuclear region of the intestinal crypt IEC-6 cells. Bioinformatics
analysis revealed clustered beta-catenin/TCF4 binding sites within the miR-30e promoter region. This promoter region was cloned
into pGL3-control luciferase reporter vector, with the enhancer region removed. Transfection of pCMV-SPORT6-beta-catenin expression
vector dose-dependently increased luciferase activity, and co-transfection of pCMV-SPORT6-TCF4 expression vector further enhanced
the promoter activity. Dexamethasone-induced IEC-6 cells differentiation caused a 2.5-fold increase in miR-30e expression,
and upon beta-catenin siRNA transfection, miR-30e increased 1.3-fold. Electrophoretic mobility shift assay and chromatin immunoprecipitation
assay confirmed the binding between beta-catenin/TCF4 complexes from IEC-6 nuclear extracts and the putative sequences in
the miR-30e promoter. These results demonstrate that beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation. 相似文献
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YOTSUYANAGI Y 《Nature》1955,176(4495):1208-1209
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