Omega-3 polyunsaturated fatty acids drive metabolite clearance to maintain brain homeostasis via activating the Glymphatic function

Dr. Huanxing Su


A common mechanism underlying neurodegenerative diseases is the accumulation of protease-resistant misfolded and aggregated proteins. The lymphatic circulation plays a very important role in the clearance of extracellular proteins and excess fluid from the interstitium, which is critical to tissue or organ homeostasis and function. Recent studies have demonstrated an organ-wide anatomic structure in the brain termed as “the Glymphatic system” that facilitates the efficient lymphatic clearance of extracellular solutes from the parenchyma. Advancing age and brain injury cause impaired glymphatic clearance, which contributes to the loss of homeostasis of neuronal environment. Therefore, driving metabolite clearance from the brain via activating the Glymphatic System represents a novel therapeutic strategy for the treatment of neurodegenerative diseases. We show that omega-3 polyunsaturated fatty acids (PUFAs) significantly promote interstitial Aβ clearance from the brain and resist Aβ injury. Imaging on clarified brain tissues clearly displayed that omega-3 PUFAs markedly inhibit the activation of astrocytes and well protect the AQP4 polarization in the affected brain region after Aβ injection. The results of our studies provide evidence that the function of the brain clearance system could be regulated by a pharmacological agent and omega-3 PUFAs exert beneficial effects via activating the Aβ clearance system in the brain.