NEUROPROTECTION PROTECTS AGAINST CELLULAR APOPTOSIS, NEURAL STROKE DAMAGE, ALZHEIMER'S DISEASE AND RETINAL DEGENERATION

摘要

A unique DHA product, 10, 17S-docosatriene ("Neuroprotectin D1" or "NPD1"), was found to provide surprisingly effective neuroprotection when administered right after an experimental stroke. Moreover, both nerve cells and retinal pigment epithelial (RPE) cells were found to synthesize 10,175-docosatriene (NPD 1) from DHA. NPD 1 also potently counteracted H2O2/TNFalpha oxidative stress-mediated cell apoptotic damage. Under the same oxidative-stress conditions, NPDI up-regulated the anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-xL, and decreased expression of the pro-apoptotic proteins, Bad and Bax. Moreover, in RPE cells NPD1 inhibited oxidative stress-induced caspase-3 activation, IL-lß-stimulated human COX-2 promoter expression, and apoptosis due to N-retinylidene-N-retinylethanolamine (A2E). Overall, NPD1 protected both nerve and retinal pigment epithelial cells from cellular apoptosis and damage due to oxidative stress. NPD1 concentration in the brain of Alzheimer's patients was found to be significantly decreased from that of controls. In cultured human brain cells, NPD1 synthesis was up-regulated by neuroprotective soluble ß amyloid, and NPD 1 was found to inhibit secretion of toxic ß amyloid peptides.