| First Author | Hung SY | Year | 2015 |
| Journal | Neuropharmacology | Volume | 93 |
| Pages | 243-51 | PubMed ID | 25686800 |
| Mgi Jnum | J:345203 | Mgi Id | MGI:6835172 |
| Doi | 10.1016/j.neuropharm.2015.02.003 | Citation | Hung SY, et al. (2015) LC3 overexpression reduces Abeta neurotoxicity through increasing alpha7nAchR expression and autophagic activity in neurons and mice. Neuropharmacology 93:243-51 |
| abstractText | Autophagy is an intracellular degradation pathway with dynamic interactions for eliminating damaged organelles and protein aggregates by lysosomal digestion. The EGFP-conjugated microtubule-associated protein 1 light chain 3 (EGFP-LC3) serves to monitor autophagic process. Extracellular beta-amyloid peptide accumulation is reported as a major cause in Alzheimer's disease (AD) pathogenesis; large numbers of autophagic vacuoles accumulate in patients' brains. We previously demonstrated that extracellular Abeta (eAbeta) induces strong autophagic response and alpha7nAChR acts as a carrier to bind with eAbeta; which further inhibits Abeta-induced neurotoxicity via autophagic degradation. In the present study, we overexpressed LC3 in both neuroblastoma cells (SH-SY5Y/pEGFP-LC3) and mice (TgEGFP-LC3) to assess the effect of LC3 overexpression on Abeta neurotoxicity. SH-SY5Y/pEGFP-LC3 cells and primary cortical neuron cultures derived from E17 (embryonic day 17) TgEGFP-LC3 mice showed not only better resistance against Abeta neurotoxicity but also higher alpha7nAChR expression and autophagic activity than control. Administration of alpha-bungarotoxin (alpha-BTX) to block alpha7nAChR antagonized the neuroprotective action of SH-SY5Y/pECGF-LC3 cells, suggesting that eAbeta binding with alpha7nAChR is an important step in Abeta detoxification. LC3 overexpression thus exerts neuroprotection through increasing alpha7nAChR expression for eAbeta binding and further enhancing autophagic activity for Abeta clearance in vitro and in vivo. |
