PubMed:15192323 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/15192323","sourcedb":"PubMed","sourceid":"15192323","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/15192323","text":"APP induces neuronal apoptosis through APP-BP1-mediated downregulation of beta-catenin.\nAlzheimer's disease (AD) is a neurodegenerative disease associated with progressive dementia. This mini-review focuses on how the amyloid precursor protein (APP) plays a central role in AD and Down syndrome as the regulator of the APP-BP1/hUba3 activated neddylation pathway. It is argued that the physiological function of APP is to downregulate the level of beta-catenin. However, this APP function is abnormally amplified in patients with familial AD (FAD) mutations in APP and presenilins, resulting in the hyperactivation of neddylation and the decrease of beta-catenin below a threshold level. Evidence in the literature is summarized to show that dysfunction of APP in downregulating beta-catenin may underlie the mechanism of neuronal death in AD and Down syndrome.","tracks":[{"project":"test_HZAU_BioNLP","denotations":[{"id":"T1","span":{"begin":0,"end":3},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T2","span":{"begin":39,"end":42},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T3","span":{"begin":218,"end":243},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T4","span":{"begin":245,"end":248},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T5","span":{"begin":319,"end":322},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T6","span":{"begin":412,"end":415},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T7","span":{"begin":476,"end":479},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T8","span":{"begin":561,"end":564},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T9","span":{"begin":757,"end":760},"obj":"https://www.uniprot.org/uniprot/P05067"}],"attributes":[{"subj":"T1","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T2","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T3","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T4","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T5","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T6","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T7","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T8","pred":"source","obj":"test_HZAU_BioNLP"},{"subj":"T9","pred":"source","obj":"test_HZAU_BioNLP"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"15192323-2#137#144#gene8883","span":{"begin":319,"end":326},"obj":"gene8883"},{"id":"15192323-2#145#150#gene9039","span":{"begin":327,"end":332},"obj":"gene9039"},{"id":"15192323-2#99#112#diseaseC0013080","span":{"begin":281,"end":294},"obj":"diseaseC0013080"},{"id":"15192323-5#69#72#gene351","span":{"begin":757,"end":760},"obj":"gene351"},{"id":"15192323-5#54#65#diseaseC3887505","span":{"begin":742,"end":753},"obj":"diseaseC3887505"},{"id":"15192323-5#152#154#diseaseC0002395","span":{"begin":840,"end":842},"obj":"diseaseC0002395"},{"id":"15192323-5#159#172#diseaseC0013080","span":{"begin":847,"end":860},"obj":"diseaseC0013080"}],"relations":[{"id":"137#144#gene888399#112#diseaseC0013080","pred":"associated_with","subj":"15192323-2#137#144#gene8883","obj":"15192323-2#99#112#diseaseC0013080"},{"id":"145#150#gene903999#112#diseaseC0013080","pred":"associated_with","subj":"15192323-2#145#150#gene9039","obj":"15192323-2#99#112#diseaseC0013080"},{"id":"69#72#gene35154#65#diseaseC3887505","pred":"associated_with","subj":"15192323-5#69#72#gene351","obj":"15192323-5#54#65#diseaseC3887505"},{"id":"69#72#gene351152#154#diseaseC0002395","pred":"associated_with","subj":"15192323-5#69#72#gene351","obj":"15192323-5#152#154#diseaseC0002395"},{"id":"69#72#gene351159#172#diseaseC0013080","pred":"associated_with","subj":"15192323-5#69#72#gene351","obj":"15192323-5#159#172#diseaseC0013080"}],"attributes":[{"subj":"15192323-2#137#144#gene8883","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15192323-2#145#150#gene9039","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15192323-2#99#112#diseaseC0013080","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15192323-5#69#72#gene351","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15192323-5#54#65#diseaseC3887505","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15192323-5#152#154#diseaseC0002395","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15192323-5#159#172#diseaseC0013080","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"test_HZAU_BioNLP","color":"#ec939a","default":true},{"id":"DisGeNET5_gene_disease","color":"#93b4ec"}]}]}}