Interaction of apoNeuroglobin with heme–Aβ complexes relevant to Alzheimer’s disease

Abstract

Heme–Aβ complexes are known to produce toxic partially reduced oxygen species (PROS), catalyze oxidation of neurotransmitters and have been associated with Alzheimer’s disease (AD). Neuroglobin (Ngb) play a crucial neuroprotective role against oxidative damage, hypoxic injuries, stroke and apoptosis of neuronal cells. In this study, the interaction of heme–Aβ with apoNeuroglobin (apoNgb) has been investigated using a combination of spectroscopic techniques. Absorption and resonance Raman data confirm that apoNgb can uptake heme from heme–Aβ and constitute a six-coordinate low-spin ferric heme-active site identical to that of Ngb. ApoNgb can also uptake heme from reduced heme–Aβ resulting in the formation of ferrous Ngb. The rate of the heme transfer reaction has been found to be of the order of 10⁶ M⁻¹ s⁻¹. The reaction is faster for oxidized heme–Aβ than the reduced form. The amount of PROS formation by heme–Aβ complexes has been found to diminish drastically after reaction with apoNgb. ApoNgb can also sequester ligand-bound heme from heme–Aβ, e.g., the CO-bound heme from heme–Aβ–CO complex resulting in the formation of Ngb–CO complex. Additionally, ApoNgb can sequester heme from self-assembled monolayer (SAM) of surface-bound heme–Aβ formed over Au surface. This heme sequestration by apoNgb from heme–Aβ not only diminishes heme-induced toxicity but more significantly it produces Ngb which has well-documented neuroprotective role and can thereby potentially reduce risks associated with AD.

Graphical Abstract