Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The multifunctional, anti-Alzheimer drug, ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] combines the neuroprotective effects of the anti-Parkinson drug, rasagiline, a selective monoamine oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of rivastigmine in a single molecule. Ladostigil has been shown to possess potent antiapoptotic and neuroprotective activities in various oxidative insults in vitro and in vivo, such as prevention of the fall in mitochondrial membrane potential and regulation of Bcl-2 family proteins. In the present study, we demonstrate that ladostigil (1 microM) increased cell viability, associated with the increase of catalase activity and decrease of intracellular reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells exposed to (hydrogen peroxide) H(2)O(2). Furthermore, ladostigil significantly elevated mRNA levels of the antioxidants enzymes, catalase, NAD(P)H quinone oxidoreductase 1 (NQO1) and peroxiredoxin 1 (Prx 1) in H(2)O(2)-treated SH-SY5Y cells. Chronic treatment with ladostigil (1 mg/kg gavage per day for 30 days) markedly up-regulated mRNA expression levels of various antioxidant enzymes in aged rat hippocampus (e.g. glutathione peroxidase precursor (GSHPX-P), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD)). These findings indicate that in addition to its multiple neuroprotective characteristics, ladostigil also possesses antioxidant properties, which might be beneficial for the treatment of oxidative stress (OS) in aging and age-associated neurodegenerative diseases.
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PMID:The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity. 1859 87

The current therapeutic advance in which future drugs are designed to possess varied pharmacological properties and act on multiple targets has stimulated the development of the multimodal drug, ladostigil (TV3326; (N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate). Ladostigil combines neuroprotective effects with monoamine oxidase (MAO)-A and MAO-B and cholinesterase (ChE) inhibitory activities in a single molecule, as a potential treatment for Alzheimer's disease (AD) and Lewy body disease. In the present study, we demonstrate that ladostigil (10(-6)-10 muM) dose-dependently increased cell viability, associated with increased activity of catalase and glutathione reductase and decrease of intracellular reactive oxygen species production in a cytotoxic model of human SH-SY5Y neuroblastoma cells exposed to hydrogen peroxide (H(2)O(2)). In addition, ladostigil significantly upregulated mRNA levels of several antioxidant enzymes (catalase, NAD(P)H quinone oxidoreductase 1 and peroxiredoxin 1) in both H(2)O(2)-treated SH-SY5Y cells, as well as in the high-density human SK-N-SH neuroblastoma cultured apoptotic models. In vivo chronic treatment with ladostigil (1 mg/kg per os per day for 30 days) markedly upregulated mRNA expression levels of various enzymes involved in metabolism and oxidation processes in aged rat hippocampus. In addition to its unique combination of ChE and MAO enzyme inhibition, these results indicate that ladostigil displays neuroprotective activity against oxidative stress-induced cell apoptosis, which might be valuable for aging and age-associated neurodegenerative diseases.
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PMID:The novel cholinesterase-monoamine oxidase inhibitor and antioxidant, ladostigil, confers neuroprotection in neuroblastoma cells and aged rats. 1875 29

The widespread use of pesticides in agriculture represents a threat to the human populations exposed to them. In this cross-sectional study, the hematological and biochemical parameters, plasma cholinesterase (PChE) activity, oxidative stress, genotoxicity, and NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism were measured in 100 greenhouse workers occupationally exposed to pesticide mixture and 104 normal healthy controls. There was a decrease in erythrocytes (5.45%, p = 0.026) and hemoglobin (3.26%, p = 0.025), and an increase in mean corpuscular hemoglobin (3.54%, p = 0.013) in the exposed workers. Sprayers showed a reduction in PChE (23%) and GSH (50%) levels, and an increase in lipid peroxidation (LPO) (55%), protein carbonyl (145%), Superoxide dismutase activity (61%), and total antioxidant capacity (35%) (p < 0.001 for all parameters but LPO: p = 0.009). Genotoxicity parameters were significantly high in the exposed cases (for all parameters: p < 0.001 but tail length: p = 0.002). There was a significant correlation between oxidative stress and genotoxicity parameters, and also between these biomarkers and PChE activity. The NQO1 C609T polymorphism was not significantly associated with studied biomarkers. The findings indicate that occupational exposure to a mixture of pesticides can induce hematotoxicity, oxidative stress, and genotoxicity in greenhouse workers.
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PMID:Hematological Abnormality, Oxidative Stress, and Genotoxicity Induction in the Greenhouse Pesticide Sprayers; Investigating the Role of NQO1 Gene Polymorphism. 2941 80