According to the research, cellular antiviral defence mechanisms are disrupted by a particular gene variation that affects the mitochondria. The data suggest that in individuals with genetic vulnerability, viral infections may cause or alter the symptoms of neurological disorders.
The key findings were published in the journal Nature.
There are still unresolved questions about what type of triggers may be involved and why a disease emerges at a particular age. The cellular hubs for energy and nutrition metabolism, the mitochondria, appear to have taken on new, significant responsibilities in shielding cells from environmental and internal threats. Crucially, it has been established that mitochondria have a unique role in bolstering the immune system; nevertheless, it remains uncertain how relevant these activities are to human illnesses.
According to the current study, brain disorders and occasionally liver malfunction are linked to impaired mitochondrial functioning in the immune system. Under the direction of academy professor Anu Suomalainen, a multidisciplinary team found that a genetic variation altering the mitochondrial POLG enzyme’s activity delays the detection of viral infection, delaying a severe inflammatory response that damages the liver and brain.
The POLG variation transmitted to populations of European descent from a single person that dates back to the Viking era. High carrier frequencies are seen in Northern European nations in particular: one in 100 people in Finland and Norway. MIRAS, or mitochondrial recessive ataxia syndrome, is a neurological condition that appears in a person who receives the POLG-variant from both parents. The question of whether MIRAS is caused by other causes arises from the wide variation in the ages at which the disease first appears and manifests.
The group demonstrates that the POLG variation causes a delayed, hyperactive immune response to viral infection, which damages the liver and brain, as well as a weaker initial immunological activation in response to the infection using a variety of model systems. According to the experts, this process explains why some MIRAS patients present as severe epileptic teenagers, while other individuals with the same genetic background display illness symptoms years or even decades later, such as Parkinson’s disease or abnormalities in motor coordination.
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Our results indicate that external factors, such as viral infections, can modify manifestation and age-of-onset of neurological diseases.
Identification of susceptibility factors and triggering mechanisms are valuable targets for new therapy developments. The current findings indicate the importance of new mitochondrial functions in maintaining brain health.
Yilin Kang, postdoctoral scientist
Source: University of Helsinki News
Journal Reference: Kang, Yilin, et al. “Ancestral Allele of DNA Polymerase Gamma Modifies Antiviral Tolerance.” Nature, 2024, pp. 1-10, https://doi.org/10.1038/s41586-024-07260-z.
