SNCA and Parkinson disease: In vitro and in vivo studies have shown that SIRT2 mediates exacerbation of alpha-synuclein toxicity in models of PD.298 NAD + metabolism is altered in sporadic PD patient-derived cells, which contributes to SIRT2 activation and subsequent decrease in the levels of acetylated α-tubulin.297 These results suggest that SIRT2 deletion was protective in PD models.