Exercise and smoking: health rivals revealing shared protective mechanisms in Parkinson's?

Compelling epidemiological evidence suggests that exercise and smoking are modifiable risk factors that are linked to a reduced risk of Parkinson's disease. These two risk factors represent opposite ends of a spectrum: exercise is universally embraced, while smoking is rightly eschewed for its established adverse health effects. Yet, intriguingly, preclinical evidence suggests that at their biological cores, exercise and some of the many components of tobacco may share strikingly similar working mechanisms that may favorably modify PD risk or disease course, for which definitive evidence is still lacking. Here, we deconstruct these overlapping and putative neuroprotective mechanisms. Our aim is to transform this unexpected overlap into an actionable perspective toward identifying novel targets for disease-modifying therapies that can slow the progression of Parkinson's disease, and to inspire novel translational efforts in disease modification in PD. We stress that while both factors may theoretically inform disease-modifying strategies for PD, in practice, only exercise should be promoted for its health benefits, whereas smoking remains firmly contraindicated due to its known detrimental health effects.