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

作者：Choudhary Sinjan^*; Save Shreyada N; Vavilala Sirisha L^*

来源：Scientific Reports, 2018, 8(1): 5692.

DOI：10.1038/s41598-018-24079-7

alpha-Synuclein (alpha-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 alpha-Syn fibrillation and dissolution of preformed alpha-Syn fibrillar structures through a combination of spectroscopic and microscopic techniques. The kinetics of alpha-Syn fibrillation demonstrates that Cr-SPs are very effective in inhibiting alpha-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 alpha-Syn and delay the conversion of alpha-helical intermediate into beta-sheet rich structures. Cr-SPs are also effective even if onset of alpha-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.

• 出版日期2018-4-9