Unravelling the inhibitory activity of Chlamydomonas reinhardtii sulfated polysaccharides against α-Synuclein fibrillation

Abstract

α-Synuclein (α-Syn) is an intrinsically disordered presynaptic protein, whose aggregation is critically involved in Parkinson’s disease (PD). Many of the currently available drugs for the treatment of PD are not sufficiently effective in preventing progress of the disease and have multiple side-effects. With this background, efficient drug candidates, sulfated polysaccharides from Chlamydomonas reinhardtii (Cr-SPs) were isolated and investigated for their effect on inhibition of α-Syn fibrillation and dissolution of preformed α-Syn fibrillar structures through a combination of spectroscopic and microscopic techniques. The kinetics of α-Syn fibrillation demonstrates that Cr-SPs are very effective in inhibiting α-Syn fibrillation. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis gel-image shows presence of soluble protein in the presence of Cr-SPs after completion of the fibrillation process. The morphological changes associated with fibrillation monitored by transmission electron microscopy showed that Cr-SPs efficiently bind with α-Syn and delay the conversion of α-helical intermediate into β-sheet rich structures. Cr-SPs are also effective even if onset of α-Syn fibrillation has already started and they also have the ability to dissolve pre-formed fibrils. Thus, the current work has substantial therapeutic implications towards unlocking the immense potential of algal products to function as alternative therapeutic agents against PD and other protein aggregation related disorders.

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

“…Some polysaccharides have been shown to stimulate neuroprotective effects in vivo, in different models for neurodegeneration [19]. Interestingly, a green algae polysaccharide was shown to have anti-PD activity through inhibition of α-Synuclein fibrillation [20,21]. Anti-PD activity was also recently determined for natural polysaccharides via increasing cellular autophagy [22].…”

Inhibitory properties of microalgal extracts on thein vitroreplication of cyprinid herpesvirus 3

“…However, while no analysis of the extract composition of C. reinhardtii was performed in this work, there is some data published in peer-reviewed literature regarding bioactive compounds contained in extracts of this species. For example, Choudhary et al (2018) determined that ethanolic aqueous extracts of C. reinhardtii consisted to almost 70 % of carbohydrates with a high sulphate content, based on which the existence of sulphated polysaccharides in this green alga could be proven afterwards (Choudhary et al 2018;Kamble et al 2018;Vishwakarma et al 2019). In addition, Yao et al (2015) showed a high content of glycolipids for isopropanolic C. reinhardtii extracts.…”

Transthyretin Anti-Amyloidogenic and Fibril Disrupting Activities of Bacopa monnieri (L.) Wettst (Brahmi) Extract

“…In aqueous environments, ANS has a weak fluorescence and displays an emission of maximum at 500 nm. Upon binding to the hydrophobic patches of proteins it produces a blue shift in its emission wavelength and an increase in its fluorescence intensity the extent of which is dependent on the protein structure and milieu surrounding ANS [27]. In the presence of human TTR tetramer, ANS binds specifically to the thyroxine-binding sites within the hydrophobic cavity with a consequent increase in fluorescence intensity at about 480 nm [28].…”