Investigations carried out by researchers at the German Center for Neurodegenerative Diseases (DZNE) suggest that genetic remnants of viruses present in the human genome could have an impact on the development of neurodegenerative diseases. This discovery, featured in the journal Nature Communications, is based on studies conducted on cell cultures. The researchers propose that these endogenous retroviruses could potentially contribute to the spread of abnormal protein aggregates that are characteristic of certain forms of dementia, such as Alzheimer’s disease and frontotemporal dementia.
While it has long been suspected that viral infections play a role in the genesis and progression of neurodegenerative diseases, the DZNE scientists have identified a mechanism that does not require infection by external pathogens. Instead, it points to the presence of endogenous retroviruses that have naturally accumulated in the human DNA over evolutionary processes. Normally, these retroviruses remain dormant, but there is evidence to suggest that they can be activated under certain conditions and contribute to the development of cancer and neurodegenerative diseases.
In their study, the researchers focused on two specific endogenous retroviruses, HERV-W and HERV-K, which are known to be activated in multiple sclerosis, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia. Using cell cultures, they simulated the production of proteins from these retroviruses’ envelopes and discovered that these viral proteins facilitated the transport of tau aggregates between cells. Tau aggregates are small clumps of proteins that accumulate in the brains of individuals affected by neurodegenerative diseases.
The researchers found that the viral proteins acted as mediators for the transport of tau aggregates, as they integrated into cell membranes and the membranes of extracellular vesicles. These vesicles are tiny fat bubbles that are naturally secreted by cells. The fusion of membranes facilitated by the viral proteins allowed the tau aggregates to spread more easily between cells.
The activation of endogenous retroviruses could be linked to changes in gene regulation as part of the natural aging process. Neurodegenerative diseases often manifest in older individuals. This raises two potential approaches to therapy. The first involves suppressing gene expression to inactivate the endogenous retroviruses. The second approach focuses on neutralizing the viral proteins, potentially through the use of antibodies. The researchers believe that dementia patients with tau aggregates may have increased levels of these antibodies, which could be isolated, reproduced, and used to develop a passive vaccine.
In addition to antibody-based treatments, the researchers are also considering the use of antiviral drugs. They have already observed in cell culture experiments that such drugs can halt the spread of protein aggregates.
The researchers at DZNE, in collaboration with their colleagues in Berlin and Bonn, plan to search for specific antibodies in patients with neurodegenerative diseases. This research could provide insights into potential therapeutic targets. The study also highlights the possibility of using antiviral drugs to disrupt the progression of neurodegenerative diseases.
The discovery of the role played by endogenous retroviruses in the development of neurodegenerative diseases opens up new avenues for research and the development of targeted therapies. It represents an important step towards better understanding the underlying mechanisms of these diseases and potentially finding ways to prevent or slow down their progression.
