Viral Infections May Promote Alzheimer's Like Diseases: Study

Add as a preferred source on Google

Some viral diseases may possibly contribute to neurodegenerative diseases such as Alzheimer's and Parkinson's disorder, according to a study.

The research, published in the journal Nature Communications, is based on laboratory experiments that showed that certain viral molecules facilitate the intercellular spreading of protein aggregates that are hallmarks of brain diseases.

The team led by researchers at the University of Bonn in Germany noted that aggregates of misfolded proteins, which occur in so-called prion disease have the ability to pass from one cell to another, where they transfer their abnormal shape to proteins of the same kind.

As a result, they said, the disease spreads across the brain. A similar phenomenon occurs in Alzheimer's and Parkinson's disease, which also exhibit assemblies of misfolded proteins, according to the researchers. Transmission of aggregates could involve direct cell-to-cell contact, the release of "naked" aggregates into extracellular space or packaging in vesicles, which are tiny bubbles surrounded by a lipid envelope that is secreted for communication between cells.

"The precise mechanisms of transmission are unknown," said Ina Vorberg, a professor at the University of Bonn.

"However, it is an obvious guess, that aggregate exchange by both direct cell contact and via vesicles depends on ligand-receptor interactions," Vorberg said.

The researchers need that this is because, in both scenarios, membranes need to make contact and fuse. This is facilitated when ligands are present that bind to receptors on the cell surface and then cause the two membranes to fuse, they said. The researchers performed an extensive series of studies with different cell cultures.

They investigated the intercellular transfer of either prions or aggregates of tau proteins, as they occur in similar forms in prion diseases or Alzheimer's disease.

Mimicking what happens as a result of viral infection, the researchers induced cells to produce viral proteins that mediate target cell binding and membrane fusion.

Two proteins were chosen as prime examples: SARS-CoV-2 spike protein S, which stems from the virus causing COVID-19, and vesicular stomatitis virus glycoprotein VSV-G, which occurs in a pathogen that infects cattle and other animals.

Cells expressed receptors for these viral proteins, namely the LDL receptor family, which act as docking ports for VSV-G, and human ACE2, the receptor for the spike protein.

"We could show that the viral proteins are incorporated both into the cellular membrane and into the extracellular vesicles," Vorberg said.

"Their presence increased protein aggregate spreading between cells, both by direct cell contact or by extracellular vesicles," he added.

The viral ligands mediated an effective transfer of aggregates into recipient cells, where they induced new aggregates. "The ligands act like keys that unlock the recipient cells and thus sneak in the dangerous cargo," Vorberg said.

"Certainly, our cellular models do not replicate the many aspects of the brain with its very specialised cell types, she added. However, independent of the tested cell type producing the pathologic aggregates, the presence of viral ligands clearly increased the spreading of misfolded proteins to other cells.

Overall, the data suggest that viral ligand-receptor interactions can in principle affect the transmission of pathologic proteins. "The brains of patients suffering from neurodegenerative diseases sometimes contain certain viruses. They are suspected to cause inflammation or to have a toxic effect, thus accelerating neurodegeneration," Vorberg said.

"However, viral proteins could also act differently: They could increase the intercellular spreading of protein aggregates already ongoing in neurodegenerative diseases like Alzheimer's," she added.

Disclaimer: The information provided in this article is for general informational and educational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or a qualified healthcare provider with any questions you may have regarding a medical condition.