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Article

Review Article

Exp Neurobiol 2015; 24(2): 95-102

Published online May 11, 2015

https://doi.org/10.5607/en.2015.24.2.95

© The Korean Society for Brain and Neural Sciences

Control of Inflammatory Responses: a New Paradigm for the Treatment of Chronic Neuronal Diseases

Joo Hong Woo1, Jee Hoon Lee1, Hyunmi Kim1,2, Soo Jung Park1, Eun-hye Joe1,2, and Ilo Jou1,2*

1Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea.

2Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-721, Korea.

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-31-219-5061, FAX: 82-31-219-5069
e-mail: jouilo@ajou.ac.kr
Present address: Department of Pharmacology, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 443-749 Rep. of Korea.

Received: March 9, 2015; Revised: April 30, 2015; Accepted: April 30, 2015

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.

Keywords: inflammation, JAK-STAT, nuclear receptor, liver X receptor, post-transcriptional regulation, MKP-1