UniProt UniProt http://www.uniprot.org Mock publication and experiment for abstract interactions that are not interaction evidences. Mock publication and experiment for abstract interactions that are not interaction evidences. unspecified method Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine 2008 imex curation Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-brain-cortex Homo sapiens brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] confocal microscopy confocal microscopy immunohistochemistry immunohistochemistry Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease Brain tissues taken from the temporal cortex (temporal pole, including Brodmann area 38, which is the apparent rostral origin of the superior, middle and inferior temporal gyri) and hippocampus from individuals with Alzheimer's disease sdy1@columbia.edu Accepted 2019-JUL-17 AT 17:22 BST AT 17:22 BST by MGT Nature medicine 2008 imex curation Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine 2008 imex curation Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brain-cortex Mus musculus brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] confocal microscopy confocal microscopy immunohistochemistry immunohistochemistry Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease Mice overexpressing a mutant form of human amyloid precursor protein sdy1@columbia.edu Accepted 2019-JUL-17 AT 17:22 BST AT 17:22 BST by MGT Nature medicine 2008 imex curation Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine 2008 imex curation Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu Accepted 2019-JUL-17 AT 17:22 BST AT 17:22 BST by MGT Nature medicine 2008 imex curation Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine 2008 imex curation Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-brain-cortex Homo sapiens brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease Brain tissues taken from the temporal cortex (temporal pole, including Brodmann area 38, which is the apparent rostral origin of the superior, middle and inferior temporal gyri) and hippocampus from individuals with Alzheimer's disease sdy1@columbia.edu Accepted 2019-JUL-17 AT 17:22 BST AT 17:22 BST by MGT Nature medicine 2008 imex curation Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine 2008 imex curation Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-brain-cortex Homo sapiens brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] electron microscopy electron microscopy Electron crystallography Electron cryomicroscopy Electron crystallography Electron cryomicroscopy antibody detection identification by antibody antibody detection Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease Immunogold electron microscopy with gold-conjugated antibodies to Ab42 (18-nm gold particles) and CypD (12-nm gold particles). Brain tissues taken from the temporal cortex (temporal pole, including Brodmann area 38, which is the apparent rostral origin of the superior, middle and inferior temporal gyri) and hippocampus from individuals with Alzheimer's disease sdy1@columbia.edu Accepted 2019-JUL-17 AT 17:22 BST AT 17:22 BST by MGT Nature medicine 2008 imex curation Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine 2008 imex curation Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brain-cortex Mus musculus brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu Accepted 2019-JUL-17 AT 17:22 BST AT 17:22 BST by MGT Nature medicine 2008 imex curation Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine 2008 imex curation Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease sdy1@columbia.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brain-cortex Mus musculus brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] electron microscopy electron microscopy Electron crystallography Electron cryomicroscopy Electron crystallography Electron cryomicroscopy antibody detection identification by antibody antibody detection Du H., Guo L., Fang F., Chen D., Sosunov AA., McKhann GM., Yan Y., Wang C., Zhang H., Molkentin JD., Gunn-Moore FJ., Vonsattel JP., Arancio O., Chen JX., Yan SD. Alzheimers - Interactions investigated in the context of Alzheimers disease Mice overexpressing a mutant form of human amyloid precursor protein Immunogold electron microscopy with gold-conjugated antibodies to Ab42 (18-nm gold particles) and CypD (12-nm gold particles). sdy1@columbia.edu Accepted 2019-JUL-17 AT 17:22 BST AT 17:22 BST by MGT Nature medicine 2008 imex curation a4_human Amyloid-beta precursor protein APP A4 AD1 Alzheimer disease amyloid protein ABPP PreA4 Cerebral vascular amyloid peptide Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN DIP protein P05067 original sequence version: 160 DIP protein P05067 original sequence version: 207 DIP protein P05067 original sequence version: 185 DIP protein P05067 original sequence version: 188 A12EE761403740F5 ppid_human Peptidyl-prolyl cis-trans isomerase D Cyclophilin-40 Cyclophilin-related protein PPID CYP40 CYPD Rotamase D 40 kDa peptidyl-prolyl cis-trans isomerase protein protein human Homo sapiens Human MSHPSPQAKPSNPSNPRVFFDVDIGGERVGRIVLELFADIVPKTAENFRALCTGEKGIGHTTGKPLHFKGCPFHRIIKKFMIQGGDFSNQNGTGGESIYGEKFEDENFHYKHDREGLLSMANAGRNTNGSQFFITTVPTPHLDGKHVVFGQVIKGIGVARILENVEVKGEKPAKLCVIAECGELKEGDDGGIFPKDGSGDSHPDFPEDADIDLKDVDKILLITEDLKNIGNTFFKSQNWEMAIKKYAEVLRYVDSSKAVIETADRAKLQPIALSCVLNIGACKLKMSNWQGAIDSCLEALELDPSNTKALYRRAQGWQGLKEYDQALADLKKAQGIAPEDKAIQAELLKVKQKIKAQKDKEKAVYAKMFA DIP protein Q08752 original sequence version: 106 39D4100748B35D48 p05067-pro_0000000092 Amyloid-beta protein 42 Alzheimer disease amyloid protein Cerebral vascular amyloid peptide APP A4 AD1 ABPP PreA4 Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA 672 713 3AC85563D7858C37 ppid_mouse Peptidyl-prolyl cis-trans isomerase D Ppid Rotamase D 40 kDa peptidyl-prolyl cis-trans isomerase Cyclophilin-40 protein protein mouse Mus musculus Mouse MSHASPAAKPSNSKNPRVFFDVDIGGERVGRIVLELFADIVPKTAENFRALCTGEKGTGSTTGKPLHFKGCPFHRIIKKFMIQGGDFSNQNGTGGESIYGEKFEDENFHYKHDREGLLSMANAGPNTNGSQFFITTVPTPHLDGKHVVFGQVIKGLGVARTLENVEVNGEKPAKLCVIAECGELKEGDDWGIFPKDGSGDSHPDFPEDADIDLKDVDKILLISEDLKNIGNTFFKSQNWEMAIKKYAKVLRYVDSSKAVIEKADRSRLQPIALSCVLNIGACKLKMSNWQGAIDSCLEALEMDPSNTKALYRKAQGWQGLKEYDQALADLKKAQEIAPGDKAIQAELLKVKQMIKAQKDKEKAVYAKMFA mint PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides 32891716E9113438 p05067-pro_0000000093 Amyloid-beta protein 40 APP A4 AD1 ABPP Alzheimer disease amyloid protein Cerebral vascular amyloid peptide PreA4 Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV 672 711 D563D7858C3768F1 a4_mouse Amyloid-beta precursor protein App Alzheimer disease amyloid A4 protein homolog ABPP Amyloidogenic glycoprotein Amyloid precursor protein A4 AD1 Alzheimer disease amyloid protein Amyloid-beta (A4) precursor protein Amyloid-beta A4 protein protein protein mouse Mus musculus Mouse MLPSLALLLLAAWTVRALEVPTDGNAGLLAEPQIAMFCGKLNMHMNVQNGKWESDPSGTKTCIGTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHTHIVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDSVDSADAEEDDSDVWWGGADTDYADGGEDKVVEVAEEEEVADVEEEEADDDEDVEDGDEVEEEAEEPYEEATERTTSTATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCVPFFYGGCGGNRNNFDTEEYCMAVCGSVSTQSLLKTTSEPLPQDPDKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPHHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHPFGVDSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFGHDSGFEVRHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN 988D89E089092A3E ppid-app-1 4 11 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role bait bait purified purified direct interaction direct interaction Fig. 1B/C app-ppid-2 4 13 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role bait bait purified purified direct interaction direct interaction Fig. 1A/C abeta_42_oligomer_human-ppid-1 4 23 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role bait bait purified purified direct interaction direct interaction Fig. 1E abeta_40_oligomer_human-ppid-1 4 27 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role bait bait purified purified direct interaction direct interaction Fig. 1D We first examined the interaction of CypD with Aβ by surface plasmon resonance (SPR) ppid-app-2 5 11 unspecified role unspecified role prey prey physiological level physiological level endogenous level endogenous endogenous endogenous level 13 unspecified role unspecified role prey prey physiological level physiological level endogenous level endogenous endogenous endogenous level 10 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level association association Fig. 1G To determine whether CypD and Aβ actually interact in pathophysiologically relevant settings, we subjected mitochondrial proteins to immunoprecipitation with an antibody to CypD followed by immunoblotting with an antibody to Aβ. ppid-app-3 7 12 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level 9 unspecified role unspecified role prey prey engineered engineered physiological level physiological level endogenous level endogenous endogenous endogenous level P05067:p.Lys670_Met671delinsAsnLeu mutation mutation certain certain sequence position certain certain certain sequence position certain KM NL Tue Mar 19 12:08:10 GMT 2019 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Lys670Asn;Met671Leu]' Tue Jun 30 19:08:47 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys670_Met671delinsAsnLeu' P05067:p.Val717Phe mutation mutation certain certain sequence position certain certain certain sequence position certain V F Tue Jun 30 18:13:16 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Val717Phe' physical association physical association Fig. 1I, 4C Interaction not observed in CypD-deficient transgenic mice overexpressing a mutant form of human amyloid precursor protein (mAPP-Ppif-/-), CypD-null (Ppif-/-) or nontransgenic mice. ppid-app-4 2 11 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 10 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level colocalization colocalization Fig. 2A app-ppid-1 6 11 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 10 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level colocalization colocalization Fig 2C, Supp. Fig. 3A ppid-app-5 3 12 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 9 unspecified role unspecified role neutral component neutral component engineered engineered physiological level physiological level endogenous level endogenous endogenous endogenous level P05067:p.Lys670_Met671delinsAsnLeu mutation mutation certain certain sequence position certain certain certain sequence position certain KM NL Tue Mar 19 11:20:06 GMT 2019 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Lys670Asn;Met671Leu]' Tue Jun 30 18:41:44 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys670_Met671delinsAsnLeu' P05067:p.Val717Phe mutation mutation certain certain sequence position certain certain certain sequence position certain V F Tue Jun 30 18:22:06 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Val717Phe' colocalization colocalization Fig. 2B app-ppid-3 8 12 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 9 unspecified role unspecified role neutral component neutral component engineered engineered physiological level physiological level endogenous level endogenous endogenous endogenous level P05067:p.Lys670_Met671delinsAsnLeu mutation mutation certain certain sequence position certain certain certain sequence position certain KM NL Tue Mar 19 11:05:12 GMT 2019 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Lys670Asn;Met671Leu]' Tue Jun 30 19:30:40 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys670_Met671delinsAsnLeu' P05067:p.Val717Phe mutation mutation certain certain sequence position certain certain certain sequence position certain V F Tue Jun 30 16:11:39 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Val717Phe' colocalization colocalization Figure 2D, Supp. Fig. 3G ppid-app-6 7 12 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level 14 unspecified role unspecified role prey prey physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Supp Fig 5A Amyloid-beta 42 peptide Interaction only observed when cells are treated with amyloid-beta 42 peptide and not observed in Ppif-/- mice abeta-42-oligomer_human pre-fibrillar amyloid-beta oligomer prefibrillar amyloid-beta oligomer Type 2 amyloid-beta oligomer fibrillar amyloid-beta oligomer Annular protofibril complex Amyloid-beta fibrils beta-amyloid protein 42 heterooligomer beta-amyloid protein 42 complex beta-amyloid-42 complex beta amyloid protein 42 complex amyloid-beta-42 complex amyloid beta protein 42 complex amyloid-beta protein 42 heterooligomer amyloid-beta-42 heterooligomer amyloid beta protein 42 heterooligomer beta-amyloid-42 heterooligomer beta amyloid protein 42 heterooligomer Abeta protein 42 complex Amyloid-beta protein 42 oligomeric complex APP oligomer Type 1 amyloid-beta oligomer ADDL complex 11 unspecified role unspecified role protein 42 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 11 unspecified role unspecified role protein 42 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 60 58 direct interaction direct interaction human Homo sapiens Human stable complex stable complex biological system reconstruction evidence based on paralogy evidence used in manual assertion biological system reconstruction evidence based on paralogy evidence used in manual assertion Protein complex involved in modulation of signaling and synaptic function in the brain, predominantly in the cerebral cortex and hippocampus. This oligomer of protein 42 only has positive neurogenetic effects by activating synaptic protein kinases. May have a role in depressing synaptic activity thus preventing excitotoxicity. Influences synaptic plasticity through various receptors, including NMDAR, mGluR and alpha7 nicotinic acetylcholine receptors (CPX-236). Mediates dendritic spine loss leading to decreased synapse density, inhibition of long-term potentiation (LTP), enhancement of long-term depression (LTD), excessive calcium influx, mitochondrial impairment, endoplasmic reticulum stress and activation of apoptotic processes. May bind plasma membrane lipids affecting their stability and leading to cytotoxicity. May affect metal ion homeostasis by chelating synaptic copper, zinc or iron ions. Mostly found in the extracellular space with a small proportion occurring as membrane-bound species. Dimers (CPX-1062) and oligomers of soluble amyloid-beta peptides are the main pathogenic species linked to Alzheimer's disease. Cellular prion protein (PrPC/PRNP, P04156) binds amyloid-beta oligomers mediating their synaptic dysfunction. Insoluble fibrils and plaques form during the latter stages of the disease. Chaperones, such as alphaB-crystallins or clusterin (P10909), bind to misfolded oligomeric species and form long-lived complexes, thereby preventing both their further growth into fibrils and their dissociation into synaptotoxic dimers. Amyloid-beta peptide may act as transcription factor for its own precursor protein APP and its cleavage enzyme BACE1 (P56817) initiating a positive feedback mechanism that ultimately leads to amyloidogenesis and Alzheimer's disease. Heterooligomer Alzheimers disease [EFO:0000249]: a progressive, neurodegenerative disease characterized by loss of function and death of nerve cells in several areas of the brain leading to loss of cognitive function such as memory and language, starting in late middle age or in old age. Marked histologically by the degeneration of brain neurons especially in the cerebral cortex and by the presence of neurofibrillary tangles and plaques containing beta-amyloid. Many forms of amyloid-beta oligomers exist in a dynamic equilibrium: from low-n amyloid-beta oligomer complexes such as dimers and trimers to high-n amyloid-beta oligomer complexes, such as pre-fibrilar and fibrilar oligomers to inactive fibrils. Pre-fibrilar oligomers form random coils and beta-turns and fibrils and oligomeric fibrils form anti-parallel beta-sheets. The oligomers are inherently thermodynamically more stable than the dimers. Barbara Kramarz, ARUK-UCL Accepted 2017-MAY-25 by ORCHARD abeta-40-oligomer_human pre-fibrillar amyloid-beta oligomer prefibrillar amyloid-beta oligomer Type 2 amyloid-beta oligomer fibrillar amyloid-beta oligomer Annular protofibril complex Amyloid-beta fibrils beta-amyloid protein 40 homooligomer beta-amyloid protein 40 complex beta-amyloid-40 complex beta amyloid protein 40 complex amyloid-beta-40 complex amyloid beta protein 40 complex amyloid-beta protein 40 homooligomer amyloid-beta-40 homooligomer amyloid beta protein 40 homooligomer beta-amyloid-40 heterooligomer beta amyloid protein 40 homooligomer Abeta protein 40 complex Amyloid-beta protein 40 oligomeric complex APP oligomer Type 1 amyloid-beta oligomer ADDL complex 13 unspecified role unspecified role protein 40 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 13 unspecified role unspecified role protein 40 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 62 64 direct interaction direct interaction human Homo sapiens Human stable complex stable complex biological system reconstruction evidence based on paralogy evidence used in manual assertion biological system reconstruction evidence based on paralogy evidence used in manual assertion Protein complex involved in modulation of signaling and synaptic function in the brain, predominantly in the cerebral cortex and hippocampus. May have a role in depressing synaptic activity thus preventing excitotoxicity. Influences synaptic plasticity through various receptors, including NMDAR, mGluR and alpha7 nicotinic acetylcholine receptors (CPX-236). Mediates dendritic spine loss leading to decreased synapse density, inhibition of long-term potentiation (LTP), enhancement of long-term depression (LTD), excessive calcium influx, mitochondrial impairment, endoplasmic reticulum stress and activation of apoptotic processes. May bind plasma membrane lipids affecting their stability and leading to cytotoxicity. May affect metal ion homeostasis by chelating synaptic copper, zinc or iron ions. Mostly found in the extracellular space with a small proportion occurring as membrane-bound species. Dimers (CPX-1069) and oligomers of soluble amyloid-beta peptides are the main pathogenic species linked to Alzheimer's disease. Cellular prion protein (PrPC/PRNP, P04156) binds amyloid-beta oligomers mediating their synaptic dysfunction. Insoluble fibrils and plaques form during the latter stages of the disease. Chaperones, such as alphaB-crystallins or clusterin (P10909), bind to misfolded oligomeric species and form long-lived complexes, thereby preventing both their further growth into fibrils and their dissociation into synaptotoxic dimers. Amyloid-beta peptide may act as transcription factor for its own precursor protein APP and its cleavage enzyme BACE1 (P56817) initiating a positive feedback mechanism that ultimately leads to amyloidogenesis and Alzheimer's disease. Homooligomer Alzheimers disease [EFO:0000249]: a progressive, neurodegenerative disease characterized by loss of function and death of nerve cells in several areas of the brain leading to loss of cognitive function such as memory and language, starting in late middle age or in old age. Marked histologically by the degeneration of brain neurons especially in the cerebral cortex and by the presence of neurofibrillary tangles and plaques containing beta-amyloid. Many forms of amyloid-beta oligomers exist in a dynamic equilibrium: from low-n amyloid-beta oligomer complexes such as dimers and trimers to high-n amyloid-beta oligomer complexes, such as pre-fibrilar and fibrilar oligomers to inactive fibrils. Pre-fibrilar oligomers form random coils and beta-turns and fibrils and oligomeric fibrils form anti-parallel beta-sheets. The oligomers are inherently thermodynamically more stable than the dimers. Barbara Kramarz, ARUK-UCL Accepted 2017-JUL-25 by ORCHARD