<h3>Title</h3>
<p><span style="color: #0000ff;">Systematic investigation of toxicity linked parameters of amyloid oligomers</span></p>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p style="text-align: justify;">Parkinson’s disease, Type II diabetes etc.) suggest that the intermediate soluble oligomers (which form during the process of aggregation) are key players in the disease. Decades of extensive research has failed to provide a clear mechanism of disease progression. Here, we have tried to understand a few toxicity-linked parameters of two amyloid peptides by using two completely different approaches. For amyloid beta (Abeta, responsible for Alzheimer's disease), we came across a mysterious interaction in its N-terminus. It was manifested in the form of a short lifetime component of an attached dye (rhodamine-B) in cultured rat neuronal cell line which made it toxic. We found a transient interaction of Abeta with a lipid carrier protein apoE that changes its conformation. We validated this observation in primary rat astrocyte cells and also in patient ipsc derived neural stem cells providing a strong correlation between the short lifetime and Alzheimer’s disease. On the other hand, we tried to understand the molecular arrangements of individual oligomers of amylin (responsible for type II diabetes) in a model lipid bilayer. Using a method Q-SLIP that we recently developed, and by using quencher labelled lipids, we found that the monomeric arrangement in the oligomers are very different from the self-replicative arrangement observed in mature amyloid fibrils. This may explain why they are more toxic than the fibrils.</p>