Unraveling the proteins that cause neurodegenerative diseases

Many neurodegenerative conditions, including Parkinson’s disease, Alzheimer’s disease and type II diabetes, result from abnormal protein clusters that block biochemical signaling in the body. To find new treatments for these devastating illnesses, researchers are looking at physical biology to identify ways of preventing protein clusters from forming. A new model reveals the kinetics of how these clusters form and identifies particles that act like barriers to stop cluster formation.

In the model, Malhotra and Babu set out to explore the conditions that lead to colloidal spheres, the first protein tangles that end in the debilitating clusters. They examined the role of solvent condition and patch size on the behavior of colloidal (“B”) particles. By tuning these conditions, the team was able to control the structure of the cluster-forming proteins.

The model reveals how mobile obstacles (M particles) form an irreversible, unbreakable bond with the patchy part of B particles but form a weak, reversible bond with the non-patchy part of B particles. According to Babu, the model results reduced the number of neighbor particles by a factor of 5.36. Because the bonded M-particle occupies the spaces between the proteins, it inhibits the formation of linear chains, limiting the opportunities for clustering.

The model results are reminiscent of peptide P4, which is associated with insulin fiber inhibition. Babu believes these results could lead to new approaches to treat many neurodegenerative diseases.

Source: “Mobile obstacles accelerate and inhibit the bundle formation by two-patch colloidal particles,” by Isha Malhotra and Sujin B. Babu, The Journal of Chemical Physics (2019). The article can be accessed at https://doi.org/10.1063/1.5110777 .