The Novel Neuroprotective Compound KMS99220 Has an Early Anti-neuroinflammatory Effect via AMPK and HO-1, Independent of Nrf2

• DOI: 10.5607/en.2018.27.5.408
• Publication Date: 2018-11-06T08:59:46Z
• Authors: Ji Ae Lee; Hye Ri Kim; Jiyoung Kim; Ki Duk Park; Dong Jin Kim; Onyou Hwang
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Original Article

We have previously reported a novel synthetic compound KMS99220 that prevented degeneration of the nigral dopaminergic neurons and associated motor deficits, suggesting neuroprotective therapeutic utility for Parkinson's disease. Microglia are closely with neuroinflammation, which plays key role in pathogenesis neurodegenerative diseases. In this study, we investigated effects on signaling involving AMP-activated protein kinase (AMPK) heme oxygenase-1 (HO-1), enzymes thought to regulate inflammation. was shown elevate enzyme activity purified AMPK, phosphorylation cellular AMPK BV2 microglia. It increased level HO-1, attenuated by inhibitors. lowered IκB, nuclear translocation NFκB, induction inducible nitric oxide synthase, generation cells had been challenged lipopolysaccharide. This anti-inflammatory response involved because both its pharmacological inhibition knockdown expression abolished response. The inhibitors also reversed KMS99220. HO-1 occurred within 1 h, appeared not involve transcription factor Nrf2, Nrf2 did affect compound's inducing- time window. These findings indicated leads AMPK-induced microglia, turn an important early signaling. Together property, may serve as feasible agent against neuroinflammation neurodegeneration.