Protein hydration dynamics play a key role in the aggregation of several proteins, which is a preliminary step to various neurodegenerative diseases. Thus, the aggregation process could be detected in time by detecting the changing dynamics of the water network and modulated using inactive substances that serve as a vehicle or medium for the drug or other active substance. Understanding debilitating neurodegenerative diseases at the molecular level is critical to finding treatments or solutions. A phenomenon called “liquid phase separation” (LLPS) underlines the formation of cell organelles such as P bodies, nucleoli, which are membraneless compartments in the cytoplasm of cells.
LLPS, a self-aggregating system, is an intermediate step in the formation of stable protein aggregates. When multivalent proteins interact, they undergo a rapid transformation from small complexes to large polymeric assemblies with increasing protein concentration. This dense phase often resembles liquid droplets exhibiting higher protein density and weaker molecular motion than the surrounding medium. This process, initiated by liquid phase transfer, plays a key role in causing human diseases, especially age-related neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and cataracts. Understanding the phase separation process at the molecular level has therefore become a new area of ​​research in the molecular biology fraternity.
Scientists at the S.N Bose National Center for Basic Sciences, an autonomous institute of the Department of Science and Technology (DST), investigated how protein hydration changes when LLPS sets in. Scientists have noticed the essential role of water in the liquid. liquid phase separation, which is the key to neurodegenerative diseases. They found that some excipients or inactive substances that serve as a vehicle or medium for the drug or other active ingredient, such as sucrose, can stabilize LLPS, while some can inhibit it. Thus, the aggregation process of these diseases could be modulated by changing the dynamics of the water network using these excipients.
In an article published in J. Phys. Chem. Let the scientists under the guidance of prof. Rajib Kumar Mitra to examine four excipients — arginine, glucose, ubiquitin and bovine serum albumin. Certain excipients such as sucrose have been found to stabilize the LLPS process, while bovine serum albumin (BSA) inhibits the process. Their experiments revealed that hydration of both proteins and excipients is important in regulating the LLPS process. Therefore, monitoring the change in hydration could act as a potential marker for the early and easy detection of the onset of LLPS.
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