Unraveling the Mystery of IAPP Amyloids: How 'Aged' Protein Plaques Impact Toxicity and Disease
"New research sheds light on how the characteristics of human islet amyloid polypeptide (IAPP) amyloids change over time, impacting their toxicity and potential role in diseases like type 2 diabetes."
For years, scientists have been intensely studying amyloid proteins, particularly their role in diseases like Alzheimer's and type 2 diabetes. These proteins, when misfolded, aggregate into structures known as amyloid fibrils, which are believed to contribute to cellular damage. While much is understood about the initial stages of fibril formation, less is known about how these fibrils change as they age and whether those changes alter their impact on the body.
A new study published in Science Bulletin is diving deeper into this question, specifically focusing on human islet amyloid polypeptide (IAPP) amyloids. IAPP is a protein found in the pancreas that, when misfolded, forms amyloid plaques associated with the development of type 2 diabetes. The researchers sought to understand how the physical and toxicological properties of these IAPP amyloids evolve over time.
This article breaks down the key findings of this research, explaining how the characteristics of IAPP amyloids change as they 'age,' how these changes influence their toxicity and ability to seed new amyloid formations, and what this all means for potential therapeutic strategies. Ultimately, this research suggests that understanding the long-term behavior of amyloid plaques is crucial for tackling related diseases.
The Changing Face of Amyloids: What Happens as They Age?
The research team aged IAPP fibrils for up to two months and then examined their physical and biological properties. Surprisingly, they found that as IAPP fibrils aged, their toxicity actually decreased. This was an unexpected finding, as many assume amyloid plaques become more harmful over time.
- Atomic Force Microscopy: Used to probe the mechanical properties of IAPP fibrils at different ages, revealing comparable stiffness but age-dependent fragmentation.
- Sonication: Fibrils were broken down using sound waves, and the resulting fragments self-assembled into large lamellar structures, the largest reported to date.
- Blue-Native PAGE: This technique showed that older IAPP amyloids had an increased capacity to bind to other proteins, which might explain their ability to sequester fresh IAPP.
Implications for Future Treatments: A New Perspective on Amyloid Diseases
This research provides a new perspective on the role of amyloid plaques in diseases like type 2 diabetes. The finding that aged IAPP amyloids can sequester toxic IAPP and reduce its harmful effects suggests that targeting these plaques might not always be the best approach.
Instead, future therapies might focus on preventing the initial misfolding and aggregation of IAPP, or on enhancing the ability of aged plaques to sequester toxic IAPP. Understanding the dynamic structural and toxicity profiles of amyloid fibrils and plaques, as this study highlights, is crucial for developing effective treatments.
While this study focused on IAPP amyloids in type 2 diabetes, the researchers suggest that the findings may be applicable to other amyloid proteins and related diseases, such as Alzheimer's. Further research is needed to fully understand the implications of these findings, but this study represents an important step forward in unraveling the complexities of amyloid diseases.