Understanding Protein Aggregation May Aid Quest for Better Alzheimer’s Treatments

Understanding Protein Aggregation May Aid Quest for Better Alzheimer’s Treatments
Better understanding the mathematics behind how protein clumps form — and how therapies interfere with this process — may improve treatment strategies for Alzheimer’s, and other diseases, new research suggests. The study, "Optimal control strategies for inhibition of protein aggregation," was published in PNAS. Protein aggregation is the term for when proteins — usually misfolded ones —  form clumps. This process is thought to play a role in a number of diseases, particularly Alzheimer's and Parkinson's. But even though "proteins forming clumps" sounds like a simple process, it involves a number of steps. First, there is primary nucleation, in which a few individual proteins come together to form a fibril — basically a little strand of proteins linked together. The fibril then grows longer as more proteins are added. The process of fibril formation and growth can take a long time (years or even decades), which may explain why Alzheimer's typically is seen only in older people. Once the fibrils reach a critical mass, secondary nucleation begins. Once there are enough clumps, more clumps start forming faster and faster, growing at an exponential rate. The researchers behind the new study used this understanding of the physics of protein aggregation in combination with control theory (a framework for understanding systems that are constantly changing) to make predictions about how different treatments would affect
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