Song, Xiao-Min Yu, Qian Dong, Xin Yang, Hyun Ok Zeng, Ke-Wu Li, Jun Tu, Peng-Fei 2024-01-20T00:33:55Z 2024-01-20T00:33:55Z 2021-09-05 2017-09 1567-5769 https://pubs.kist.re.kr/handle/201004/122345 Microglia-mediated neuroinflammation is a key risk factor to the development of Alzheimer' disease (AD). Aldose reductase (AR) has been found to be widely involved in inflammation-related diseases; however, whether aldose reductase inhibitors (ARIs) could be used to treat neuroinflammation is rarely reported. This study aims to evaluate the anti-neuroinflammatory effects of two major ARIs of Sorbinil (Sor) and Zopolrestat (Zol) in beta-amyloid protein (A beta)-induced microglia (BV-2). We find that Sor and Zol significantly inhibit TNF-alpha, IL-1 beta, IL-6 production from microglia in response to All stimulation. Mechanism study showed that Sor and Zol decreased the production of intracellular ROS which resulted in an effective inhibition on the phosphorylation of several protein kinase C (PKC) isoforms including PKC alpha/beta, delta, zeta/lambda and mu. Moreover, Sor and Zol inactivated PCKassociated IKK beta-I kappa B-NF-kappa B and mitogen-activated protein kinase (JNK, p38, ERK) inflammation pathways. In summary, our findings suggest that Sor and Zol could inhibit A beta-induced neuroinflammation by regulating ROS/ PKC-dependent NF-kappa B and MAPK signaling pathways, indicating that ARIs could be promising agents for treating inflammation-related neurodegenerative diseases such as AD. English ELSEVIER PROTEIN-KINASE-C ENDOTOXIN-INDUCED UVEITIS INFLAMMATORY RESPONSE PHOSPHOLIPASE-C ACTIVATION MICROGLIA EXPRESSION TRANSCRIPTION GROWTH CELLS Aldose reductase inhibitors attenuate beta-amyloid-induced TNF-alpha production in microlgia via ROS-PKC-mediated NF-kappa B and MAPK pathways Article 10.1016/j.intimp.2017.06.005 1 INTERNATIONAL IMMUNOPHARMACOLOGY, v.50, pp.30 - 37 INTERNATIONAL IMMUNOPHARMACOLOGY 50 30 37 scie scopus 000408073200005 2-s2.0-85020742617 Immunology Pharmacology & Pharmacy Immunology Pharmacology & Pharmacy Article PROTEIN-KINASE-C ENDOTOXIN-INDUCED UVEITIS INFLAMMATORY RESPONSE PHOSPHOLIPASE-C ACTIVATION MICROGLIA EXPRESSION TRANSCRIPTION GROWTH CELLS Neuroinflammation beta-Amyloid Aldose reductase inhibitor Sorbinil Zopolrestat