Funded Studies
Objective/Rationale:
Cigarette smoking is associated with a lower risk of Parkinson’s disease (PD), but its protective mechanism is unknown. Tobacco mosaic virus (TMV), a plant pathogen infecting more than 150 different plants (i.e. tobacco, tomatoes, peppers, and cucumbers), is present on cigarettes and in smokers’ saliva. Researchers recently found that humans have antibodies against TMV and smokers have a higher level of anti-TMV antibodies in blood serum than non-smokers. This study will test the hypothesis that anti-TMV antibodies play a protective role in development of PD.
Project Description:
Researchers will collect serum samples from four groups: 1) non-smoker PD patients, 2) smoker PD patients, 3) non-smoker healthy controls, and 4) smoker healthy controls. They will measure and compare the levels of anti-TMV antibodies in serum. If a lower level of the antibody is found in PD patients, especially non-smoker PD patients, they will then investigate the pathway of the protective effect of the antibody on PD at cellular and molecular levels.
Using bioinformatics, the scientists found that the protein TOMM40L (a channel-forming protein involved in the importation of proteins into mitochondria) contains a strong sequence ancestry to the TMV coat protein. Also, TOMM40L exhibits cross-reactivity with anti-TMV antibodies. Given that mitochondrial dysfunction is involved in the pathogenesis of PD, the researchers will assess whether anti-TMV antibodies can prevent PD by protecting mitochondria from malfunction.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
This study will tell researchers more about why smokers have a decreased risk of PD. These results could highlight therapeutic targets toward which scientists can develop drugs to prevent, slow or halt the disease.
Anticipated Outcome:
They expect to show that TMV-elicited specific immune responses are different between PD patients and healthy subjects and are related to their smoking status. They also expect that exposure to TMV or anti-TMV antibodies modify mitochondrial function.
Final Outcome
This study was done to determine whether an immune response to tobacco mosaic virus (TMV) in humans induced by tobacco products (i.e., smoking) is lower in PD patients. Using a sandwich ELISA assay, we measured serum anti-TMV antibodies in 73 subjects enrolled in the study (12 non-smoker PD patients, 14 smoker PD patients, 24 healthy non-smokers, and 23 healthy non-smokers). Smoker PD patients had a reduced level of serum anti-TMV antibodies than healthy smokers and this antibody level was also observed lower in non-smoker PD patients but not significantly different from healthy smokers. The serum anti-TMV levels of both smoker PD and non-smoker PD patients were similar to that of healthy non-smokers. These results showing a lower anti-TMV antibody level in PD patients suggest there is a role of TMV against Parkinson’s disease development. Our observation requires more evidence to prove and the potential mechanisms between plant viruses and Parkinson’s disease should be further explored.