Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloid precursor protein generates the beta-amyloid peptide and is a member of a multigene family that contains at least two other gene products, known as amyloid precursor-like proteins. Heme oxygenase is an enzyme whose products are antioxidant and neuroprotective. The authors report that amyloid precursor protein and amyloid precursor-like protein bind to heme oxygenase to inhibit its enzymatic activity. Our findings suggest that decreased neuroprotection caused by amyloid precursor protein-heme oxygenase interactions influences neurotoxicity in Alzheimer disease.
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PMID:Interaction of amyloid precursor proteins and heme oxygenase. 1085 Jul 33

Amyloid precursor protein (APP) generates the beta-amyloid peptide, postulated to participate in the neurotoxicity of Alzheimer's disease. We report that APP and APLP bind to heme oxygenase (HO), an enzyme whose product, bilirubin, is antioxidant and neuroprotective. The binding of APP inhibits HO activity, and APP with mutations linked to the familial Alzheimer's disease (FAD) provides substantially greater inhibition of HO activity than wild-type APP. Cortical cultures from transgenic mice expressing Swedish mutant APP have greatly reduced bilirubin levels, establishing that mutant APP inhibits HO activity in vivo. Oxidative neurotoxicity is markedly greater in cerebral cortical cultures from APP Swedish mutant transgenic mice than wild-type cultures. These findings indicate that augmented neurotoxicity caused by APP-HO interactions may contribute to neuronal cell death in Alzheimer's disease.
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PMID:Amyloid precursor proteins inhibit heme oxygenase activity and augment neurotoxicity in Alzheimer's disease. 1114 56