It has been hypothesized that neurodegeneration in PD due to decreased GM1 levels is due at least in part to a failure in trophic signaling (particularly GDNF signaling) [19, 40] and that this GM1-related failure of trophic signaling leads to depressed clearance of and accumulation of alpha-synuclein [19, 40]. This evidence concerns the gene GDNF and Parkinson disease.