N2L, a novel lipoic acid-niacin dimer protects HT22 cells against β-amyloid peptide-induced damage through attenuating apoptosis.

β-amyloid protein (Aβ) is thought to be the primary cause of the pathogenesis of Alzheimer's disease (AD). Niacin has been reported to have beneficial effects on AD. Previously, we synthesized a novel compound lipoicacid-niacin dimer (N2L) and revealed that it had potent blood-lipid regulation and antioxidative properties without aflushing effect. Given that lipid metabolism is also associated with AD, the present study aimed to investigate the neuroprotective effects of N2L on Aβ1-42-induced cytotoxicity in HT22 cells. We found that N2L significantly attenuated cell apoptosis, MDA level, ROS content, and the mitochondrial membrane potential corruption induced by Aβ1-42 in HT22 cells. In addition, the activities of SOD, GSH-px and CAT that were decreased by Aβ1-42 were also restored by N2L. Furthermore, N2L reduced proapoptotic signaling by increasing the expression of anti-apoptotic Bcl-2 and decreasing the protein expression of both pro-apoptotic Bax and cleaved Caspase-3. Together, these findings indicate that N2L holds great potential for neuroprotection against Aβ1-42-induced cytotoxicity via inhibition of oxidative stress and cell apoptosis, suggesting that N2L may be a promising agent for AD therapy.