Using cell cultures, the scientists simulated the situation in which human cells produce particular proteins from the envelope of endogenous retroviruses. Now, Vorbergs team found that the viral proteins facilitate the transportation of so-called tau aggregates from cell to cell.” Viral Transport MediatorsThe existing research study and earlier research studies by Vorbergs group recommend that viral proteins serve as transport arbitrators for tau aggregates since they place into the cell membrane and into the membrane of so-called extracellular vesicles: These are little fat bubbles that are naturally produced by cells.” For the transportation of tau aggregates from cell to cell, we see two pathways in specific. Transfer between cells that are in direct contact, and transportation within blisters that act as freight pills, so to speak, and pass from one cell to another to eventually combine with it,” Vorberg discussed.
Research recommends that endogenous retroviruses within the human genome might influence the development of neurodegenerative illness by contributing to the spread of abnormal protein aggregates in the brain. Credit: SciTechDaily.comResearchers See Ancient Genes As Potential Targets for Dementia TreatmentGenetic residues of infections that are naturally present in the human genome might impact the development of neurodegenerative illness. Scientists at DZNE come to this conclusion on the basis of research studies on cell cultures. They report on this in the journal Nature Communications. In their view, such “endogenous retroviruses” could contribute to the spread of aberrant protein aggregates– trademarks of certain dementias– in the brain. Hence, these viral antiques would be potential targets for therapies.Viral Influence on Neurodegenerative DiseasesIt has been suspected for a long time that viral infections contribute to the genesis and development of neurodegenerative diseases. Lab studies by DZNE scientists now suggest a system that, although related to infections, does not require infection by external pathogens. According to this research study, the culprits would be “endogenous retroviruses” that are naturally present in the human genome. “During evolution, genes from many infections have actually collected in our DNA.Most of these gene sequences are altered and generally muted,” described Ina Vorberg, research study group leader at DZNE and a teacher at the University of Bonn. “However, there is evidence that endogenous retroviruses are activated under particular conditions and contribute to cancer and neurodegenerative illness. Undoubtedly, proteins or other gene products stemmed from such retroviruses are discovered in the blood or tissue of patients.” Experiments With Tau AggregatesVorberg followed this trail together with associates from Bonn and Munich. Using cell cultures, the researchers simulated the scenario in which human cells produce specific proteins from the envelope of endogenous retroviruses. Particularly, this involved HERV-W and HERV K– both infections are present in the human genome however are generally dormant.However, studies show that HERV-W is activated in numerous sclerosis and HERV-K in the neurological disease “amyotrophic lateral sclerosis” (ALS) and in frontotemporal dementia (FTD). Now, Vorbergs team discovered that the viral proteins assist in the transport of so-called tau aggregates from cell to cell. “Tau aggregates” are tiny protein clumps that happen in the brains of individuals affected by certain neurodegenerative diseases– these include Alzheimers disease and FTD.” Certainly, conditions in the brain are far more intricate than our cellular model system can duplicate them. Nonetheless, our experiments show that endogenous retroviruses can influence the spread of tau aggregates in between cells,” Vorberg stated. “Endogenous retroviruses would thus not be triggers of neurodegeneration, however might fuel the illness procedure once it is currently underway.” Viral Transport MediatorsThe present research and earlier research studies by Vorbergs group recommend that viral proteins function as transport mediators for tau aggregates due to the fact that they place into the cell membrane and into the membrane of so-called extracellular vesicles: These are little fat bubbles that are naturally produced by cells.” For the transportation of tau aggregates from cell to cell, we see 2 paths in specific. Transfer in between cells that are in direct contact, and transportation within vesicles that act as cargo pills, so to speak, and pass from one cell to another to ultimately merge with it,” Vorberg discussed.” In both circumstances, membranes need to fuse. Proteins from the envelope of viruses can promote this procedure. Thats because many viruses are adjusted to fuse with host cells. This occurs by means of unique proteins that viruses continue their surfaces. If specifically these proteins are included into the cell membrane and the membrane of extracellular vesicles, it is easy to understand that the tau aggregates then spread more easily.” Starting Points for TherapyIn the course of the natural aging process, the guideline of genes can alter– originally “dormant” endogenous retroviruses might be “awakened” as an outcome. The signs of most neurodegenerative illness do not manifest till older age. This raises 2 imaginable approaches to treatment. “On the one hand, one might try to particularly reduce gene expression, that is, to suspend the endogenous retroviruses again. That would get to the root of the issue,” Vorberg stated. “But you could also start elsewhere and try to neutralize the viral proteins– for instance, with antibodies.” Searching for AntibodiesIn the viewpoint of the researchers, it is most likely that dementia clients with tau aggregates carry increased quantities of such antibodies. It may be possible to establish a passive vaccine if it were possible to isolate these and replicate them utilizing biotechnological techniques. Thus, in cooperation with DZNE associates in Berlin and Bonn, Vorbergs group intends to specifically browse for such antibodies in patients. In addition, the researchers are considering antiviral drugs. In cell culture, they have already found that such representatives can really stop the spread of protein aggregates. “This is another technique we intend to pursue,” said Vorberg.Reference: “Reactivated endogenous retroviruses promote protein aggregate spreading” by Shu Liu, Stefanie-Elisabeth Heumüller, André Hossinger, Stephan A. Müller, Oleksandra Buravlova, Stefan F. Lichtenthaler, Philip Denner and Ina M. Vorberg, 18 August 2023, Nature Communications.DOI: 10.1038/ s41467-023-40632-z.
