Benzothiazole aniline-tetra(ethylene glycol) and 3-amino-1,2,4-triazole inhibit neuroprotection against amyloid peptides by catalase overexpression in vitro

Chilumuri, Amrutha, Odell, Mark and Milton, Nathaniel G.N. (2013) Benzothiazole aniline-tetra(ethylene glycol) and 3-amino-1,2,4-triazole inhibit neuroprotection against amyloid peptides by catalase overexpression in vitro. ACS Chemical Neuroscience, 4 (11). pp. 1501-1512. ISSN 1948-7193

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Official URL: http://dx.doi.org/10.1021/cn400146a

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-? (A?), amyloid-Bri (ABri), amyloid-Dan (ADan), amylin (IAPP) and prion protein (PrP) peptides were determined. Results showed catalase overexpression was neuroprotective against A?, 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 A?, ABri, ADan, IAPP and PrP peptides. Kisspeptin 45-50 had additive neuroprotective actions against the A? peptide in catalase overexpressing cells. The effects of 3-AT had an intra-cellular site of action, whilst catalase-amyloid interactions had an extra-cellular 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.

Item Type: Article
Subjects: University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)
Depositing User: Miss Nina Watts
Date Deposited: 05 Sep 2013 10:09
Last Modified: 17 Dec 2013 16:27
URI: http://westminsterresearch.wmin.ac.uk/id/eprint/12989

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