title: Control of Inflammatory Responses: a New Paradigm for the Treatment of Chronic Neuronal Diseases.
abstract: The term 'inflammation' was first introduced by Celsus almost 2000 years ago. Biological and medical researchers have shown increasing interest in inflammation over the past few decades, in part due to the emerging burden of chronic and degenerative diseases resulting from the increased longevity that has arisen thanks to modern medicine. Inflammation is believed to play critical roles in the pathogenesis of degenerative brain diseases, including Alzheimer's disease and Parkinson's disease. Accordingly, researchers have sought to combat such diseases by controlling inflammatory responses. In this review, we describe the endogenous inflammatory stimulators and signaling pathways in the brain. In particular, our group has focused on the JAK-STAT pathway, identifying anti-inflammatory targets and testing the effects of various anti-inflammatory drugs. This work has shown that the JAK-STAT pathway and its downstream are negatively regulated by phosphatases (SHP2 and MKP-1), inhibitory proteins (SOCS1 and SOCS3) and a nuclear receptor (LXR). These negative regulators are controlled at various levels (e.g. transcriptional, post-transcriptional and post-translational). Future study of these proteins could facilitate the manipulation of the inflammatory response, which plays ubiquitous, diverse and ambivalent roles under physiological and pathological conditions.
authors.affiliation: Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Joo Hong
authors.initials: JH
authors.lastname: Woo
authors.affiliation: Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Jee Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea. ; Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Hyunmi
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea. ; Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Joe
authors.affiliation: Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea. ; Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
keywords: JAK-STAT; MKP-1; inflammation; liver X receptor; nuclear receptor; post-transcriptional regulation