In a cell free assay, the potency of Piericidin A to inhibit mitochondrial complex I is ～2 fold smaller than the one of annonacin. In cultured neurons, Piericidin A potently induces the redistribution of phosphorylated tau from the dendrites into the cell soma and induces cell death.
The viability of Tn5B1-4 cells is inhibited by Piericidin A in a time- and concentration-dependent manner with IC ₅₀ value of 0.061 μM, whilst Piericidin A shows slight inhibitory effect on the viability of HepG2 and Hek293 cells with IC ₅₀ value of 233.97 μM and 228.96 μM, respectively. Piericidin A induces apoptosis of Tn5B1-4 cells coincides with a decrease in the mitochondrial membrane potential.

Piericidin A (0.5 mg/kg/d; for 28 days via osmotic minipumps) significantly increases the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S ^+/+ mice. Piericidin A leads to increased levels of pathologically phosphorylated tau only in P301S ^+/+ mice. The synaptic density is reduced by Piericidin A treatment in P301S ^+/+ mice. Exposure to Piericidin A aggravates the course of genetically determined tau pathology.