The development of neurodegenerative diseases, such as Parkinson’s, Huntington’s, and Alzheimer’s affect millions of people every year. Previous studies have shown that an enzyme found in the endemic Herpes Simplex Virus (HSV-1); UL12.5, degrades the mitochondrial genome, which we hypothesize may predispose patients to neurodegenerative conditions. A majority of the human population is infected with HSV-1 and other herpesviridae, which encode similar enzymes, and their reactivation is commonly seen throughout life. We have found that the degradation of mitochondrial DNA by UL12.5 activity is widely conserved and when UL12.5 is expressed in the model organism, Caenorhabditis elegans (C.elegans), mitochondrial DNA content drops nearly 10-fold. Interestingly, we find that activation of the HSV-1 UL12.5 enzyme alters cellular proteostasis; the cell’s mechanism for maintaining properly folded and functional proteins. This change in proteostasis alters the aggregation of misfolded proteins, especially those involved in the cause of neurodegenerative diseases, and leads to neurological phenotypes like paralysis, which we can quantify in the worm. To study the enzymatic activity of the UL12.5, we used modified worms expressing the protein using an inducible transgene that can be verified by fluorescent microscopy. The effects of the UL12.5 activity is determined by tracking lifespan of worms, performing paralysis assays, and counting protein aggregates with controls that use a catalytically inactive version of UL12.5. We have also found that Emodin, a compound found in traditional Chinese medicine, which has previously been shown to inhibit UL12.5, alters the activity of UL12.5 in a worm model of Huntington’s disease. We hypothesize that activation of this enzyme may cause similar pathologies in the human brain and may be a causative factor in human neurodegenerative disease. Further, inhibitors of UL12.5 like Emodin may prove useful therapeutics for treating neurodegenerative diseases.