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| http://purl.uniprot.org/citations/21373759 | http://www.w3.org/2000/01/rdf-schema#comment | "Monoamine oxidase-A (MAO-A) has been associated with both depression and Alzheimer disease (AD). Recently, carriers of AD-related presenilin-1 (PS-1) alleles have been found to be at higher risk for developing clinical depression. We chose to examine whether PS-1 could influence MAO-A function in vitro. Overexpression of selected AD-related PS-1 variants (wildtype, Y115H, ΔEx9 and M146V) in mouse hippocampal HT-22 cells affects MAO-A catalytic activity in a variant-specific manner. The ability of the PS-1 substrate-competitor DAPT to induce MAO-A activity in cells expressing either PS-1 wildtype or PS-1(M146V) suggests the potential for a direct influence of PS-1 on MAO-A function. In support of this, we were able to co-immunoprecipitate MAO-A with FLAG-tagged PS-1 wildtype and M146V proteins. This potential for a direct protein-protein interaction between PS-1 and MAO-A is not specific for HT-22 cells as we were also able to co-immunoprecipitate MAO-A with FLAG-PS-1 variants in N2a mouse neuroblastoma cells and in HEK293 human embryonic kidney cells. Finally, we demonstrate that the two PS-1 variants reported to be associated with an increased incidence of clinical depression [e.g., A431E and L235V] both induce MAO-A activity in HT-22 cells. A direct influence of PS-1 variants on MAO-A function could provide an explanation for the changes in monoaminergic tone observed in several neurodegenerative processes including AD. The ability to induce MAO-A catalytic activity with a PS-1/γ-secretase inhibitor should also be considered when designing secretase inhibitor-based therapeutics."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00702-011-0616-7"xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Wei Z."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Graham B."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Rui L."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Mousseau D.D."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Pennington P.R."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Gabriel G.G."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Doig J.A."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/author | "Kuski K."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/name | "J Neural Transm (Vienna)"xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/pages | "987-995"xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/title | "Alzheimer disease-related presenilin-1 variants exert distinct effects on monoamine oxidase-A activity in vitro."xsd:string |
| http://purl.uniprot.org/citations/21373759 | http://purl.uniprot.org/core/volume | "118"xsd:string |
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