title: Benzothiazole aniline tetra(ethylene glycol) and 3-amino-1,2,4-triazole inhibit neuroprotection against amyloid peptides by catalase overexpression in vitro.
abstract: Alzheimer's disease, Familial British dementia, Familial Danish dementia, Type 2 diabetes mellitus, plus Creutzfeldt-Jakob disease are associated with amyloid fibril deposition and oxidative stress. The antioxidant enzyme catalase is a neuroprotective amyloid binding protein. Herein the effects of catalase overexpression in SH-SY5Y neuronal cells on the toxicity of amyloid-β (Aβ), amyloid-Bri (ABri), amyloid-Dan (ADan), amylin (IAPP), and prion protein (PrP) peptides were determined. Results showed catalase overexpression was neuroprotective against Aβ, ABri, ADan, IAPP, and PrP peptides. The catalase inhibitor 3-amino-1,2,4-triazole (3-AT) and catalase-amyloid interaction inhibitor benzothiazole aniline tetra(ethylene glycol) (BTA-EG4) significantly enhanced neurotoxicity of amyloid peptides in catalase overexpressing neuronal cells. This suggests catalase neuroprotection involves breakdown of hydrogen peroxide (H2O2) plus a direct binding interaction between catalase and the Aβ, ABri, ADan, IAPP, and PrP peptides. Kisspeptin 45-50 had additive neuroprotective actions against the Aβ peptide in catalase overexpressing cells. The effects of 3-AT had an intracellular site of action, while catalase-amyloid interactions had an extracellular component. These results suggest that the 3-AT and BTA-EG4 compounds may be able to inhibit endogenous catalase mediated neuroprotection. Use of BTA-EG4, or compounds that inhibit catalase binding to amyloid peptides, as potential therapeutics for Neurodegenerative diseases may therefore result in unwanted effects.
authors: Department of Human & Health Sciences and ‡Department of Molecular & Applied Biosciences, Faculty of Science & Technology, University of Westminster , 115 New Cavendish Street, London W1W 6UW, United Kingdom.
authors: Amrutha
authors: A
authors: Chilumuri
authors: Mark
authors: M
authors: Odell
authors: Nathaniel G N
authors: NG
authors: Milton
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000640:Amitrole / Q000737:chemistry / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000814:Aniline Compounds / Q000737:chemistry / Q000633:toxicity*; D052160:Benzothiazoles / Q000737:chemistry / Q000633:toxicity*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D007562:Creutzfeldt-Jakob Syndrome / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003704:Dementia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C554933:2-(4'-(dimethylamino)phenyl)benzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; C577219:CAT protein, human; D002374:Catalase; D000640:Amitrole
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