A brand new research printed within the journal Nature Communications is suggesting a novel causal link between neurodegenerative illnesses reminiscent of Alzheimer’s and an infection with the herpesvirus. The preclinical analysis signifies a deficiency in a key protein permits the virus to set off neuronal injury.
More than half a century in the past a singular speculation arose to elucidate the trigger of many neurodegenerative illnesses. The thought was viral infections could be a set off for neurodegeneration, and this gradual course of can go on for years after an acute an infection.
Known as “slow virus diseases”, the speculation linked Alzheimer’s illness with herpesvirus infections. This thought slipped to the fringes of neuroscience over the Eighties as curiosity in different causal mechanisms, such because the the amyloid speculation, finally dominated most analysis.
More just lately, following the failure of a quantity of high-profile anti-amyloid scientific trials, analysis into the connection between viral infections and neurodegeneration has elevated. Although a quantity of observational research have detected specific associations between herpes simplex virus sort I (HSV-1) and Alzheimer’s illness, direct causal mechanisms are nonetheless unclear.
This new research, led by researchers from the University of Illinois Chicago, initially got down to examine why acute HSV-1 infections could be deadly in some immunocompromised folks and innocent in lots of others. The answer got here within the type of a protein referred to as optineurin (OPTN).
“OPTN stops the virus from growing and it stops it by autophagy – engulfing the virus particles inside tiny vesicles called autophagosomes,” says Deepak Shukla, lead researcher on the project. “The autophagy that occurs may be very selective.”
After discovering the anti-viral action of OPTN in lab tests, the researchers developed a mouse model engineered to not produce the crucial protein. When these OPTN-deficient mice were infected with HSV-1 the researchers saw “striking differences in severity of infection” compared to healthy mice infected with the virus.
In mice lacking OPTN the viral infection rapidly spread into the brain and significant neurodegeneration was subsequently observed. Within 30 days of HSV-1 infection the OPTN-deficient mice started displaying notable cognitive decline.
Co-author on the new study, Chandrashekhar Patil, says OPTN deficiency was also linked to abnormal immune system activity. And this could play a part in the link between chronic herpes infections and neurodegeneration.
“The study also shows there is an impairment of immune response when there is a deficiency in OPTN,” says Patil. “OPTN is needed to signal an influx of proper immune cells at the site of infection. When you don’t have it, you have issues.”
The main discoveries in this new study are the roles OPTN plays in regulating optimal immune functions and stifling viral infections. But how much of a role this particular mechanism plays in human neurodegenerative disease is still very much unknown.
Prior studies have detected links in human patients between OPTN mutations and diseases such as amyotrophic lateral sclerosis (ALS). So it certainly is plausible OPTN dysfunction influences neurodegenerative disease but translating these findings into useful clinical treatments is still some way off.
Shukla says the next step for the research will be to investigate whether restoring optimal OPTN function can halt neurodegeneration and rescue any associated cognitive decline.
The new research was published in the journal Nature.