Fig. 7: Proposed model of the polyamine pathway and its regulation of α-Synuclein levels and toxicity.

Illustration of the PA pathway, emphasizing how the regulation of PAIE through RNAi knockdown (indicated magenta X-circles in the flow diagrams) or overexpression affects α-Syn protein levels and toxicity. The model highlights the influence of individual enzymes on polyamine metabolism, α-Syn accumulation, fly lifespan, motility, and eye integrity. The left half represents beneficial polyamine metabolism, where knockdown of ODC1, SRM, SMOX, or PAOX, or overexpression of SMOX or SAT1, reduces α-Syn levels and toxicity, promoting health and longevity. In contrast, the right half illustrates a PD-like condition, where knockdown of SMS, SAT1, ATP13A2, or SLC7A2 leads to either α-Syn accumulation or increased toxicity, ultimately resulting in neurodegeneration.