To dissect the mechanism of TREM-2 mediating Aβ-induced Rac2-iNOS complex induction

• Main Authors: Hio-Fai Cheang, 鄭曉暉
• Other Authors: Nien-Jung Chen
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/3mem9p

碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 107 === Alzheimer’s disease (AD) is the most common form of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Amyloid β (Aβ) plaques is a key player in AD. It aggregates and promotes inflammation in the brains. The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with a substantial increase risk of developing AD. TREM2 expressed on myeloid cells, such as microglia. Our previous result showed that TREM2 deficiency leads to reduce iNOS (inducible Nitric oxide synthase) expression and downstream Nitric oxide (NO) induction by oligomer Aβ (oAβ) treatment. Accordingly, protein kinase C (PKC) is a downstream signaling mediator of TREM2-Dap12 (DNAX activation protein of 12kDa) pathway. Our previous data show that Aβ-induced Rac2-iNOS complex adjoined membrane in TREM2 knockdown microglia cell, not accumulated in a perinuclear region and near the cell membrane. In addition, our previous data show that uptake and internalization of oAβ were enhanced in TREM2 deficient BMDM cells. Taken all together, we revealed a potential molecular mechanism contributed by TREM2 in the AD pathologies.