Exercise and Smoking: Yin and Yang Sharing Protective Power for 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, possibly because they both exert protective effects on neurodegeneration. Like Yin and Yang, these two risk factors represent opposite ends of a spectrum: exercise is universally embraced, while smoking is rightly eschewed. Yet, intriguingly, preclinical evidence suggests that at their biological cores, exercise and smoking may share strikingly similar working mechanisms in favorably modifying the disease course. Here, we deconstruct these overlapping and putative neuroprotective mechanisms. Our aim is to transform this unexpected overlap into an actionable perspective towards identifying novel targets for disease-modifying therapies that can slow the progression of Parkinson’s disease. 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 is firmly contraindicated due to its known detrimental health effects.