Figure 2

Possible pathophysiological mechanism implicated in PD-like pathology progression. Environmental toxins cause Complex I inhibition that in return increases ROS production inducing modification and impairing lysosomic/autophagic activity. This results in alpha-synuclein oligomerization and aggregation. Oligomerized or aggregated alpha-synuclein can i) interact with mitochondria inhibiting the mitochondrial respiratory system thereby multiplying the effect of the toxin or ii) be transported into autophagosomes and secreted to the extracellular environment inside or outside exosomes. Secreted alpha-synuclein is can be up-taken by presynaptic neurons and retrogradelly transported to the soma where it accumulates. The most important question here is. Does alpha-synuclein exert any effect on the presynaptic neurons? If so, we believe that there are two possible mechanisms: i) as an enucleating factor modifying the local alpha-synuclein and ii) impairing presynaptic mitochondria mimicking the effect of the environmental toxins on the ENS. Both possibilities could explain the progression of PD pathology as observed in patients.