title: S-nitrosylation of ApoE in Alzheimer's disease.
abstract: The mechanism by which apolipoprotein E (ApoE) isoforms functionally influence the risk and progression of late-onset Alzheimer's disease (LOAD) remains hitherto unknown. Herein, we present evidence that all ApoE isoforms bind to nitric oxide synthase 1 (NOS1) and that such protein-protein interaction results in S-nitrosylation of ApoE2 and ApoE3 but not ApoE4. Our structural analysis at the atomic level reveals that S-nitrosylation of ApoE2 and ApoE3 proteins may lead to conformational changes resulting in the loss of binding to low-density lipoprotein (LDL) receptors. Collectively, our data suggest that S-nitrosylation of ApoE proteins may play an important role in regulating lipid metabolism and in the pathogenesis of LOAD.
authors: John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Florida 33136, United States.
authors: Alexander J
authors: AJ
authors: Abrams
authors: Amjad
authors: A
authors: Farooq
authors: Gaofeng
authors: G
authors: Wang
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000378:metabolism*; D053329:Apolipoprotein E2 / Q000737:chemistry / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000737:chemistry / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000737:chemistry / Q000378:metabolism; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D020030:Nitric Oxide Donors / Q000737:chemistry; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry; D026422:S-Nitrosoglutathione / Q000737:chemistry
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D020033:Protein Isoforms; D011994:Recombinant Proteins; D026422:S-Nitrosoglutathione; D052248:Nitric Oxide Synthase Type I