Curcumin Protects β-Lactoglobulin Fibril Formation and Fibril-Induced Neurotoxicity in PC12Cells

Abstract

In this study the β-lactoglobulin fibrillation, in the presence or absence of lead ions, aflatoxin M1 and curcumin, was evaluated using ThT fluorescence, Circular dichroism spectroscopy and atomic force microscopy. To investigate the toxicity of the different form of β-Lg fibrils, in the presence or absence of above toxins and curcumin, we monitored changes in the level of reactive oxygen species and morphology of the differentiated neuron-like PC12 cells. The cell viability, cell body area, average neurite length, neurite width, number of primary neurites, percent of bipolar cells and node/primary neurite ratios were used to assess the growth and complexity of PC12 cells exposed to different form of β-Lg fibrils. Incubation of β-Lg with curcumin resulted in a significant decrease in ROS levels even in the presence of lead ions and aflatoxin M1. The β-Lg fibrils formed in the presence of lead ions and aflatoxin M1 attenuated the growth and complexity of PC12 cells compared with other form of β-Lg fibrils. However, the adverse effects of these toxins and protein fibrils were negated in the presence of curcumin. Furthermore, the antioxidant and inhibitory effects of curcumin protected PC12 cells against fibril neurotoxicity and enhanced their survival. Thus, curcumin may provide a protective effect toward β-Lg, and perhaps other protein, fibrils mediated neurotoxicity.

Inhibition of Protein Aggregation by Several Antioxidants

“…On top of that, over one hundred clinical studies have been carried out with curcumin. Searching the literature, curcumin has been shown to inhibit amyloid fibrillation of fA β [ 44 , 45 ], prion protein [ 46 ], insulin [ 47 ], hen egg white [ 48 ], lysozyme [ 49 , 50 ], and β -lactoglobulin [ 51 ]. Unfortunately, its wide application is limited due to its pharmacokinetics, which disfavors its bioavailability.…”

Modulation of ERK1/2 and Akt Pathways Involved in the Neurotrophic Action of Caffeic Acid Alkyl Esters

“…Polyphenols have been extensively studied for their antioxidant activities [2,3,4,5], and their possible role in the prevention of various pathologies such as cancer and cardiovascular disorders has been well documented [6]. Neuroprotective effects of polyphenols against various diseases of the nervous system have been addressed in a number of studies [7,8,9,10,11,12,13], and have been reported to be of therapeutic value for neurodegenerative diseases [14,15].…”

Role of dietary antioxidant (−)-epicatechin in the development of β-lactoglobulin fibrils

“…Indeed, BLG fibrils formation mechanism has been extensively investigated. BLG fibrils are usually produced by heating the protein for 24 h at 80°C, pH 2.0 and low ionic strength [7,8]. It has been shown that peptides, rather than the intact protein, are the fibrils building blocks [9].…”