Physiological Temperature Has a Crucial Role in Amyloid Beta in the Absence and Presence of Hydrophobic and Hydrophilic Nanoparticles

Abstract

Amyloid beta fibrillation can lead to major disorder of neurons processes and is associated with several neuronal diseases (e.g., Alzheimer's disease). We report here an importance of slight temperature changes, in the physiological range (35−42°C), on the amyloid fibrillation process in the presence and absence of hydrophilic (silica) and hydrophobic (polystyrene) nanoparticles (NPs). The results highlight the fact that slight increases in temperature can induce inhibitory and acceleratory effects of hydrophobic and hydrophilic NPs on the fibrillation process, respectively. Using further in vivo considerations, the outcomes of this study can be used for considerable modifications on the current diagnosis and treatment approaches in amyloid-involved diseases. KEYWORDS: Amyloid beta, fibrillation, physiological temperature, hydrophilic NPs, hydrophobic NPs T he misfolding of amyloid proteins (e.g., amyloid beta (Aβ) peptide, 1−4 prion protein, 5 α-synuclein, 6 polyglutamine, 7 glucagon, 8 and β2-microglobulin 9,10 ) followed by their fibrillation is the hallmark of over 40 human diseases, ranging from neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, Creutzfeld−Jakob disease, and Gerstmann−Straüssler− Scheinker syndrome) to non-neuropathic disorders (e.g., amyloid heart disease, rheumatoid arthritis, and type II diabetes). 11,12Among various amyloidogenic proteins, Aβ peptides are widely used as model proteins to investigate the effect of NPs on fibrillogenesis. 13 Monomeric Aβ is actually soluble in a physiological condition and has shown to be unstructured; 14 however, the fibrillar form has a characteristic cross-β structure with stacking of β strands perpendicular to the long axis of the fiber. 15−17It is well recognized that nanoparticles (NPs) have significant effect on the fibrillation process.18−20 Interestingly, it was very recently found that graphene oxide sheets (GO) with a protein corona (protein/biomolecular coated GO in biological medium 21 ) can slow amyloid the fibrillation process. 22 Although there are few reports on the effect of temperature on the kinetics of amyloid fibrillation process, 23−26 a crucial effect of slight temperature changes (i.e., in the physiological range) on the amyloid fibrillation process in the presence of NPs has not been investigated. This point is very important for the in vivo NP application to humans, specifically for treatment of amyoloid proteins (e.g., Alzheimer's and Parkinson's disease). 27 The local temperature in different brain diseases/tumors for different individuals is in the range from 33.4 to 42.0°C. 28−32 In normal body, the body temperature, during sleep, decreases and manual work leads to an increase of up to 2°C. This means that the body temperature for healthy humans varies in the range from 35 to 39°C and can find a maximum of 42°C in the case of fever. 33 Although there are significant reports on the effects of various NPs on the amyloid fibrillation process, 34−38 as far as we know there is no report on the...

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