A: Identification of inhibition of neutral sphingomyelinase 2 (nSMase2) expression, a hydrolyze that acts on the sphingolipid sphingomyelin to produce ceramide that forms extracellular vesicles. Increased levels of ceramide have been found in PD patients.D: Inhibition of nSMase2 prevents oligomeric α-synuclein aggregation in SH-SY5Y cells.R: (1) Knockdown of nSMase2 using siRNA transfection and CRISPR/Cas9 technique. (2) Protein expression by Western blot analysis targeting nSMase2 and α-synuclein. (3) Assessment of nSMase2 activity by enzyme activity assay. Here, SMPD3 is linked to Parkinson disease.