Alzheimer’s disease (AD) is the common neurodegenerative disorder characterized by the formation of extraneuronal accumulation of amyloid fibrils and intracellular neurofibrillary tangles. AD is characterized pathologically by the aggregation of Amyloid β-Protein (Aβ) into plaques. Therefore, alteration of the aggregation pathway is a promising therapeutic approach. This research is focused on using the mucilage extracted from <i>Opuntia ficus indica</i> to inhibit the formation of Aβ fibrils. Mucilage is a pectin polysaccharide with a backbone of α-D-galacturonic acid and β-L-rhamnose and a branch of arabinose or xylose. Two different fractions of mucilage can be extracted: pectin gelling extraction (GE) and non-gelling extraction (NE). Both GE and NE extracts have a similar structure but the GE extract contains higher proportion of galacturonic acid. In this work, the effectiveness of mucilage in disturbing the formation of Aβ fibrils was evaluated. Aβ monomeric species have been incubated along with different concentration of GE and NE extract <i>in vitro</i>. The aggregation kinetics of the Aβ proteins were monitored by Fourier transform infrared (FTIR) and time-resolved thioflavine-T (ThT) fluorescence spectroscopy. Transmission electron microscopy (TEM) was used to monitor the aggregation process and fibril morphology. Introducing mucilage induces changes in the secondary structures of the Aβ peptides thus interfering with protein accumulation. Our results from FTIR indicate that the mucilage interaction with aggregation intermediates results in amyloid detribalized structures. Monitoring fibril formation with ThT shows that certain concentrations of mucilage can prevent amyloid fibrils. GE extract could significantly increase the lag phase of fibril formation. More interestingly, at GE concentrations of 0.016 to 0.25 mg/mL, the fibril formation process was completely inhibited. The obtained results indicate that mucilage can disturb the protein aggregation kinetics and even inhibit the aggregation process. These experimental results support the effectiveness of cactus mucilage in the treatment of Alzheimer’s plaques.

Inhibition of formation of amyloid β-protein fibrils using cactus mucilage

251st National Meeting (2016)

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