Figure 3.

Possible and known applications of diclofenac. Diclofenac can act as an analgesic agent by activating transient outward potassium channels in neurons and simultaneously reducing the production of prostaglandins. Diclofenac can also act as a potent inhibitor of oligomerization of β-amyloid fibrils and plaque formation, which can be used in the development of therapies for diseases involving amyloid aggregation. Alternatively, diclofenac also interferes with the activation of glial cells, which may further contribute to its neuroprotective properties. Diclofenac has both inhibitory and inducing effects on cell death under different conditions. Endoplasmic reticulum stress generated by thapsigargin leads to activation of caspases and causes mitochondrial depolarization. Diclofenac suppresses the intrinsic pathway of apoptosis by interfering with caspase activation and mitochondrial depolarization. On the other hand, diclofenac treatment can result in proteasomal dysfunction generating downstream apoptotic signals such as mitochondrial cytochrome c release, causing stimulation of caspases leading to apoptosis. The pathway shown under dotted dual faced arrow curve in the top right shows the role of diclofenac in the inhibition of β-amyloid fibrils and plaque formation. The activation/formation and inhibition are depicted with arrows and blunt heads, respectively. The green color coding on arrows and blunt ends depicts the cell survival, whereas, the red color indicates cell death promoting signals.