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

Chilumuri, A., Odell, M. and Milton, N.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. https://doi.org/10.1021/cn400146a

TitleBenzothiazole aniline-tetra(ethylene glycol) and 3-amino-1,2,4-triazole inhibit neuroprotection against amyloid peptides by catalase overexpression in vitro
AuthorsChilumuri, A., Odell, M. and Milton, N.G.N.
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 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.

JournalACS chemical neuroscience
Journal citation4 (11), pp. 1501-1512
ISSN1948-7193
Year2013
PublisherAmerican Chemical Society
Digital Object Identifier (DOI)https://doi.org/10.1021/cn400146a
Publication dates
Published2013

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