Amyloid-β binds catalase with high affinity and inhibits hydrogen peroxide breakdown

Abstract

Amyloid-beta (Abeta) specifically bound purified catalase with high affinity and inhibited catalase breakdown of H(2)O(2). The Abeta-induced catalase inhibition involved formation of the inactive catalase Compound II and was reversible. Catalase<-->Abeta interactions provide rapid functional assays for the cytotoxic domain of Abeta and suggest a mechanism for some of the observed actions of Abeta plus catalase in vitro.

Model studies of cholesterol and ascorbate oxidation by copper complexes: Relevance to Alzheimer’s disease β-amyloid metallochemistry

“…In contrast, we found that catalase inhibits H 2 O 2 generation by Ab1-42/Cu immediately from the start of the reaction, when catalase activity would not be affected by time-dependent Ab1-42-mediated inhibition [47]. Furthermore, the maximal inhibition reported by Milton to be induced by Ab1-42 is 33% of the control value [48,49]. This leaves plenty of residual activity to scavenge H 2 O 2 .…”

“…Milton reported that Ab1-42 in molar excess of catalase induces a time-dependent inhibition of catalase activity [48,49]. The catalase inhibition was only detected after at least a 30 min incubation.…”

Fibril formation and toxicity of the non-amyloidogenic rat amylin peptide

“…Rat amylin 8-37 fibrils also bound catalase in a similar manner. The A␤ 31-35 fragment that has been shown to be the minimum sequence of A␤ recognized by catalase (Milton, 1999;Milton and Harris, 2009). Previous studies have demonstrated that the A␤ 31-35 peptide was able to prevent catalase binding to A␤ fibrils but not human amylin fibrils Harris, 2009, 2010).…”

“…The ability of rat amylin fibrils to interact with Congo red, a characteristic of amyloid fibrils (Klunk et al, 1999;Buxbaum and Linke, 2012), has also been assessed. Catalase binding to amyloid fibrils formed by human amylin, A␤ and the PrP has been previously documented Harris, 2009, 2010) and the region of A␤ targeted by catalase found to contain the main cytotoxic domain (Milton, 1999). We have assessed catalase binding to fibrils identified in the TEM study.…”

Axonal Transport and Mitochondrial Dysfunction in Alzheimer's Disease

“…Moreover, it has been suggested that Aβ might directly interact with specific mitochondrial and antioxidative proteins and subsequently inhibit them. For example, direct interactions with Aβ have been shown for superoxide dismutase 1 [133], catalase [134], amyloid-binding alcohol dehydrogenase [135,136] and cyclophilin D [137]. …”