Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease (AD) is a common neurodegenerative disorder, but the initiating molecular processes contributing to neuronal death are not well understood. AD is associated with elevated soluble and aggregated forms of amyloid beta (Abeta) and with oxidative stress. Furthermore, there is increasing evidence for a detrimental role of iron in the pathogenic process. In this context, iron chelation by compounds such as 3-hydroxypyridin-4-one, deferiprone (Ferriprox) may have potential neuroprotective effects. We have evaluated the possible neuroprotective actions of deferiprone against a range of AD-relevant insults including ferric iron, H(2)O(2) and Abeta in primary mouse cortical neurones. We have investigated the possible neuroprotective actions of deferiprone (1, 3, 10, 30 or 100 microM) in primary neuronal cultures following exposure to ferric iron [ferric nitrilotriacetate (FeNTA); 3 and 10 microM], H(2)O(2) (100 microM) or Abeta1-40 (3, 10 and 20 microM). Cultures were treated with deferiprone or vehicle either immediately or up to 6 h after the insult in a 24-well plate format. In order to elucidate a possible neuroprotective action of deferiprone against Parkinson's disease relevant insults another group of experiments were performed in the human neuroblastoma catecholaminergic SHSY-5Y cell line. SHSY-5Y cells were treated with MPP(+) iodide, the active metabolite of the dopaminergic neurotoxin MPTP and the neuroprotective actions of deferiprone evaluated. Cytotoxicity was assessed at 24 h by lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide turnover (FeNTA and hydrogen peroxide) and morphometric analysis of cell viability by Hoechst 33324/propidium iodide (FeNTA, Abeta and MPP(+)) or 6-carboxyfluorescein diacetate and annexin V-Cy3 (Abeta). The present study demonstrates that deferiprone protects against FeNTA, hydrogen peroxide, MPP(+) and Abeta1-40-induced neuronal cell death in vitro, which is consistent with previous in vitro and in vivo studies that have demonstrated similar protection with other iron chelators.
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PMID:Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. 1833 85

Neurotoxicant-induced elevation of intracellular calcium (Ca(2+)) and modulation by phystoestrogens were examined in vitro using human neuroblastoma SH-SY5Y cells cultured with amyloid beta-peptide (Abeta) and 1-methyl-4-phenyl-pyridine (MPP+). Although Abeta itself did not increase Ca(2+), it exacerbated the effects of carbachol. The elevation of Ca(2+) caused by the agents in combination could be reduced by pretreatment with the phytoestrogens equol and genistein, as well as by the L-type Ca(2+) channel blocker nifedipine. MPP+ exposure also elevated Ca(2+), an effect blocked by nifedipine but not by the phytoestrogens. As opposed to phytoestrogens, nifedipine was also able to significantly reduce cell death caused by higher concentrations of MPP(+) in the LDH viability assay. The results suggest that phytoestrogens are unlikely to serve as general cellular protectants for neurotoxicants with different mechanisms of action. The concentrations of Abeta and MPP(+) affecting Ca(2+) release did not inhibit cell viability as measured with the LDH release assay. This indicates that mechanisms involved with toxicity can be studied at doses that are not lethal.
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PMID:Modulation of neurotoxicant-induced increases in intracellular calcium by phytoestrogens differ for amyloid beta peptide (Abeta) and 1-methyl-4-phenyl-pyridine (MPP(+)). 1865 19