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.
Highlights
The most common therapy for PD is based on long-term dopamine (DA) replacement with 3, 4-dihydroxy-L-phenylalanine (L-DOPA), the precursor of DA; this therapy is associated with various side effects[14]
The protein and the sulphate contents were estimated to be 1.8% and 29.4%, respectively. These results clearly indicate that the extract is enriched with sulfated polysaccharides
The results suggest that the fibrillar species which are formed in the presence of Cr-sulfated polysaccharides (SPs) do not act as seeds for secondary nucleation reactions
Summary
The most common therapy for PD is based on long-term dopamine (DA) replacement with 3, 4-dihydroxy-L-phenylalanine (L-DOPA), the precursor of DA; this therapy is associated with various side effects[14]. It is known that many marine algae species contain SPs and their lower molecular weight oligosaccharide derivatives which are biocompatible, biodegradable and have been shown to offer numerous health benefits. These algal SPs have high nutritional value and pose anti-malaria, anticoagulant, anti-inflammatory, anti-viral, antiparasitic, antioxidant, anti-thrombotic and antilipidemic properties[24,25,26,27,28,29,30,31,32]. The current work is done with the objective of unlocking the immense potential of Cr-SPs to act as alternative therapeutic agents for prevention of PD and provide a scientific basis for the development of new generation of phytopharmaceuticals
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