RESUMEN
Contactin associated protein (Caspr), an adhesion molecule, plays roles in formation of paranodal junctions in myelinated axons, neurite outgrowth, synaptic plasticity in nervous system. Here we have shown a novel function of Caspr in pathogenesis of Alzheimer's disease (AD). Caspr distributes around amyloid plaques in APP/PS1 mice. Levels of Caspr increase in the cerebral cortex of 7-month-old APP/PS1 mice comparing to wild-type littermates. Caspr decreased protein levels of APP in both HEK-293 cells stably transfected with Indiana mutant APP (V717F; HEK-APP) and CHO cells which express endogenous APP, while it did not alter mRNA levels of APP. Furthermore, Caspr co-localizes and interacts with APP. Amyloid-ß (Aß) 40 and Aß42 generation were also reduced in HEK-APP cells by Caspr overexpression.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Neuronas/metabolismo , Fragmentos de Péptidos/metabolismo , Animales , Moléculas de Adhesión Celular Neuronal/genética , Regulación hacia Abajo/fisiología , Ratones , Ratones Transgénicos , Unión ProteicaRESUMEN
BACKGROUND: B(x) is a very rare ABO blood group phenotype and the molecular mechanism underlying it still remains largely unknown. This study reports two novel B(x) alleles in two Chinese individuals. STUDY DESIGN AND METHODS: Serologic investigations including serum transferase activity assay were performed with standard methods. DNA sequences of all seven exons and exon-intron boundaries of ABO gene were analyzed using genomic DNA by polymerase chain reaction and direct DNA sequencing or sequencing after gene cloning. RESULTS: B(x) phenotypes were diagnosed in these two individuals. DNA analysis revealed that the ABO gene of the two B(x) individuals was heterozygous of O01/B alleles. Two novel heterozygous mutations 905A>G and 541T>C were identified, respectively, which resulted in the amino acid changes D302G and W181R in the B glycosyltransferases. The mutations were not found in 120 randomly selected samples. CONCLUSION: Amino acid substitutions resulted from novel mutations 905A>G and 541T>C on ABO gene change highly conserved regions of the enzyme and may reduce the activity of the glycosyltransferases, leading to the B(x) phenotype.