Mechanistically, several studies report that piperine stimulates autophagic flux (via P2RX4 activation and suppression of PI3K/AKT/mTOR signaling in rodent PD models), thereby enhancing clearance of aggregated α-synuclein and reducing proteotoxic stress in substantia nigra neurons [51,52,53]. The gene discussed is SNCA; the disease is Parkinson disease.