PPARα serves as a new receptor of aspirin for neuroprotection.

Acetyl salicylic acid, commonly known as aspirin, has been being widely used as an anti-inflammatory drug for almost 100 years. However, there was no receptor known for this popular drug. Recently, we have established that peroxisome proliferator-activated receptor alpha (PPARα) acts as a novel receptor of aspirin. Activation of PPARα by aspirin stimulated a series of downstream signaling pathways that could potentially ameliorate different Alzheimer's disease (AD)-related pathologies. In this mini-review, we have discussed how aspirin-PPARα interaction plays a pivotal role in the amelioration of AD pathology via the stimulation of neurotrophic factors, upregulation of plasticity-associated genes, and removal of plaque burden in hippocampal neurons.