PubMed:9354812 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/9354812","sourcedb":"PubMed","sourceid":"9354812","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9354812","text":"Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives.\nbeta-Amyloid precursor protein (beta-APP), the source of the fibrillogenic amyloid beta-peptide (A beta) that accumulates in the brain of victims of Alzheimer's disease, is a multifunctional protein that is widely expressed in the nervous system. beta-Amyloid precursor protein is axonally transported and accumulates in presynaptic terminals and growth cones. A secreted form of beta-APP (sAPP alpha) is released from neurons in response to electrical activity and may function in modulation of neuronal excitability, synaptic plasticity, neurite outgrowth, synaptogenesis, and cell survival. A signaling pathway involving guanosine 3',5'-cyclic monophosphate is activated by sAPP alpha and modulates the activities of potassium channels, N-methyl-D-aspartate receptors, and the transcription factor NF kappa B. Additional functions of beta-APP may include modulation of cell adhesion and regulation of proliferation of nonneuronal cells. Alternative enzymatic processing of beta-APP liberates A beta, which has a propensity to form amyloid fibrils; A beta can damage and kill neurons and increase their vulnerability to excitotoxicity. The mechanism involves generation of oxyradicals and impairment of membrane transport systems (e.g., ion-motive ATPases and glutamate and glucose transporters). Genetic mutations or age-related metabolic changes may promote neuronal degeneration in Alzheimer's disease by increasing production of A beta and/or decreasing levels of neuroprotective sAPP alpha.","tracks":[{"project":"DisGeNET5_gene_disease","denotations":[{"id":"9354812-1#247#277#gene351","span":{"begin":345,"end":375},"obj":"gene351"},{"id":"9354812-1#149#168#diseaseC0002395","span":{"begin":247,"end":266},"obj":"diseaseC0002395"},{"id":"9354812-5#36#44#gene351","span":{"begin":1074,"end":1082},"obj":"gene351"},{"id":"9354812-5#94#101#diseaseC0002726","span":{"begin":1132,"end":1139},"obj":"diseaseC0002726"}],"relations":[{"id":"247#277#gene351149#168#diseaseC0002395","pred":"associated_with","subj":"9354812-1#247#277#gene351","obj":"9354812-1#149#168#diseaseC0002395"},{"id":"36#44#gene35194#101#diseaseC0002726","pred":"associated_with","subj":"9354812-5#36#44#gene351","obj":"9354812-5#94#101#diseaseC0002726"}],"attributes":[{"subj":"9354812-1#247#277#gene351","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9354812-1#149#168#diseaseC0002395","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9354812-5#36#44#gene351","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9354812-5#94#101#diseaseC0002726","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"test_HZAU_BioNLP","denotations":[{"id":"T1","span":{"begin":25,"end":50},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T2","span":{"begin":103,"end":128},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T3","span":{"begin":135,"end":138},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T4","span":{"begin":350,"end":375},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T5","span":{"begin":483,"end":486},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T6","span":{"begin":940,"end":943},"obj":"https://www.uniprot.org/uniprot/P05067"},{"id":"T7","span":{"begin":1079,"end":1082},"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"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET5_gene_disease","color":"#baec93","default":true},{"id":"test_HZAU_BioNLP","color":"#ec93d4"}]}]}}