Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloid-beta peptide (Abeta) is the toxic agent in Alzheimer's disease (AD), although the mechanism causing the neurodegeneration is not known. We previously proposed a mechanism in which excessive Abeta binds to regulatory heme, triggering functional heme deficiency (HD), causing the key cytopathologies of AD. We demonstrated that HD triggers the release of oxidants (e.g., H(2)O(2)) from mitochondria due to the loss of complex IV, which contains heme-a. Now we add more evidence that Abeta binding to regulatory heme in vivo is the mechanism by which Abeta causes HD. Heme binds to Abeta, thus preventing Abeta aggregation by forming an Abeta-heme complex in a cell-free system. We suggest that this complex depletes regulatory heme, which would explain the increase in heme synthesis and iron uptake we observe in human neuroblastoma cells. The Abeta-heme complex is shown to be a peroxidase, which catalyzes the oxidation of serotonin and 3,4-dihydroxyphenylalanine by H(2)O(2). Curcumin, which lowers oxidative damage in the brain in a mouse model for AD, inhibits this peroxidase. The binding of Abeta to heme supports a unifying mechanism by which excessive Abeta induces HD, causes oxidative damage to macromolecules, and depletes specific neurotransmitters. The relevance of the binding of regulatory heme with excessive Abeta for mitochondrial dysfunction and neurotoxicity and other cytopathologies of AD is discussed.
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PMID:Amyloid-beta peptide binds with heme to form a peroxidase: relationship to the cytopathologies of Alzheimer's disease. 1649 52

Increased activity of the subthalamic nucleus (STN) is critical in mediating motor symptoms of Parkinson's disease. To determine if altered STN activity also occurs in levodopa (L-Dopa)-unresponsive parkinsonism due to a combined nigral and striatal degeneration, metabolic activity of the STN was assessed using cytochrome oxidase (CO) histochemistry in monkeys with nigral, striatal, or nigral+striatal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and/or 3-nitropropionic acid (3NP). MPTP- and MPTP+3NP-treated monkeys had a similar parkinsonian score and were clinically indistinguishable. However, CO activity in the STN was significantly increased in MPTP-induced parkinsonism but not in MPTP+3NP-induced striatonigral degeneration. These results indicate that metabolic activity of the STN is normal following a combined nigral+striatal degeneration and may help to understand the lack of effect of STN stimulation in L-Dopa-unresponsive parkinsonism.
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PMID:Metabolic activity of the subthalamic nucleus in a primate model of L-dopa-unresponsive parkinsonism. 2081 27