On Parkinson’s trail

Scientists at a Kolkata institute find new clues to its cause

June 03, 2018 12:02 am | Updated 12:12 am IST

Despite research spread over decades, scientists are yet to figure out the cause for Parkinson’s disease, a neurodegenerative disorder. One thing is clear: the aggregation of a protein called alpha-synuclein plays a key role in development of the disease. The aggregation pathway of this protein is the subject of intense research and studies so far have focussed on protein aggregates, called amyloid fibrils, which form late in the aggregation pathway.

Researchers at the CSIR-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata, have now proposed that alpha-synuclein oligomers that come into the picture early in the aggregation pathway could be responsible for the development of Parkinson’s.

They used two amino acids to conduct their study in live neuroblastoma cells. The first one was glutamate, which happens to assist the formation of amyloid fibrils by facilitating generation of early oligomers. The second one was arginine, which inhibits amyloid fibril formation by inducing a large change in the shape of the native protein.

The study has shown that it is possible to monitor early events of the aggregation pathway when the native protein fluctuates in its monomeric states or when it forms early oligomeric molecules by using a combination of conventional methods and spectroscopy at the single molecule level.

“We have shown that it is possible to monitor and understand the early events in aggregation. It gives us hope that a therapeutic molecule may be possible against early oligomeric molecules,” says Dr. Krishnananda Chattopadhyay, leader of the research team.

“The study establishes that glutamate acts as a facilitator and arginine acts as an inhibitor of the late stage of alpha synuclein aggregation. However, it is not clear if the observed effect is because of other cellular changes due to the addition of these molecules or direct interaction of these molecules with alpha-synuclein. The mechanism of internalisation and interaction of these molecules with alpha-synuclein needs to be better understood. It will also be challenging to understand how one can transform this knowledge for drug development for a complex disease such as Parkinson’s,” says Dr. Samir K. Maji of IIT Bombay, who was not connected with the study.

Other researchers in the study included Sumanta Ghosh and Amrita Kundu of the CSIR-ICB. The research results have been published in the journal, Scientific Reports , and the work was funded by the Department of Science and Technology, Government of India.

— India Science Wire

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