Figure 1:

Schematic of the ‘triggers, facilitators and aggravators’ conceptual framework for redefining PD pathogenesis. We propose that triggers initiate disease pathogenesis during prodromal PD, and facilitators spread pathology to significantly impact the central nervous system. This results in the onset of PD motor symptoms, at which point aggravators continue to exacerbate cell loss and neuropathology, causing worsening symptoms and enabling the emergence of new symptoms. In the schematic, various suspected or validated factors have been positioned along the horizontal axis based approximately on the phase we consider they have the largest effect, and using font size which is roughly proportional to their estimated relative importance in PD pathogenesis.