EFFECTS OF BORON NITRIDE NANOTUBE ON THE SECONDARY STRUCTURE OF Aβ(1-42) TRIMER: INHIBITORY EFFECT ON AMYLOID FORMATION
Nidhi Sorouta) and Amalendu Chandrab)
Department of Chemistry, Indian Institute of Technology Kanpur, India 208016
Alzheimer Disease (AD) is the most common neurodegenerative disorder formed by amyloids which are highly ordered cross-β sheet protein aggregates deposits in various parts of the human brain [1]. The mechanism underlying the aggregation of amyloid fibrils is not fully understood till now. Recent studies indicate that the trimer and tetramer species of Aβ(1-42) is the most neurocytotoxic forms of low molecular weight (LMW) oligomers which bound with the neurons and causing their cell death [3]. The ultimate goal in this study is to find the ways of preventing Aβ(1-42)-trimerisation process and their fibril formation. In many studies people searched for short peptides and proteins or small organic molecules to treatment of AD but because of the issue of blood-brain barrier (BBB) permeability researchers are not able to use these designed proteins to make therapeutic agents. Some of the experimental and theoretical studies showed that carbon nanotubes (CNTs), graphene, fluorinated nanoparticles, fullerene prevent the fibril formation. Although these carbonaceous nanoparticles are commonly used but there is a huge disadvantage because these are cytotoxic for our body [4]. Therefore, a search for safe and biocompatible nanomaterial is required. BNNTs are nontoxic for health and environment and biocompatible in living cells [5]. Experimentally we have only a limited structural information about the Aβ(1-42) trimer because of their transient nature. Here the effect of boron nitride nanotube on the structure and dynamics of Aβ(1-42) trimer has been investigated through all atom molecular dynamics simulation for 1 µs. Our results indicates that due to the polar nature of boron nitride nanotubes, it keeps the peptides of Aβ(1-42) trimer separated and prevents their self-aggregation. It is also stabilized the helical structure of each peptide monomer. Thus here our study reflects the inhibition of amyloid aggregation by kinetically trapped mechanism with stabilization of the helix as mentioned earlier [2].
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a)E-mail: nidhic[at]iitk.ac.in, b)E-mail: amalen[at]iitk.ac.in