Helicobacter Protein Inhibits Amyloid Formation

A recent study has unveiled significant findings regarding the role of certain strains of Helicobacter pylori in inhibiting amyloid formation, a process linked to various neurodegenerative diseases.

Amyloids are aggregates of proteins that can exhibit either functional roles, such as in bacterial biofilms, or pathogenic characteristics, as seen in conditions like Alzheimer's disease, Parkinson's disease, and type 2 diabetes. Researchers from the Karolinska Institute in Huddinge, Sweden, led by Zhen Jin, have discovered that an extracellular protein produced by H. pylori demonstrates a strong anti-amyloid effect, effectively preventing the aggregation of proteins associated with both bacterial and human pathologies. These findings were published in the scientific journal Science Advances.

The protein of interest is known as CagA (cytotoxin-associated gene A), which is not expressed by all strains of H. pylori. Previous research has indicated that CagA-positive strains can alter the diversity and composition of the gut microbiota, but the underlying mechanisms remained unclear until now.

The Swedish researchers established that CagA inhibits the formation of amyloids and biofilms. They isolated and characterized the N-terminal fragment of CagA (CagAn, consisting of amino acids 1 to 884), which contains three domains primarily made up of numerous ?-helices.

Functional studies demonstrated that CagAn effectively inhibits the formation of Pseudomonas biofilms. Additionally, it was found to suppress the pathogenic amyloid formation caused by proteins such as A?, Tau, ?-Synuclein, and Amylin (also referred to as islet amyloid polypeptide or IAPP), which is secreted alongside insulin from the pancreatic ?-cells. Remarkably, just 20 nM of CagAn significantly extended the half-life of A?42 fibrillation from 1.5 hours to 14 hours, indicating a substantial slowdown in fibril formation. Similar strong inhibitory effects were observed with other substrates, such as 30 µM ?-Synuclein when treated with 500 nM of CagAn.

These discoveries may pave the way for novel therapeutic strategies targeting amyloid diseases by utilizing the properties of CagA, potentially leading to innovative treatments for conditions like Alzheimer's and Parkinson's.