Pathological studies on Parkinson’s disease (PD) patients suggest that PD pathology progresses from the
enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously
shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression
pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this
progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of
alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic
sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly
suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the
transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would
have crucial implications in the strategies used to prevent and treat PDThis work was
supported by the Fritz-Thyssen Foundation, theGerman Parkinson’s disease Society and by
Amelia Jimenez Gomez as private dono
