생화학분자생물학회

	Kwon-Yul Ryu( kyryu@uos.ac.kr )
	2017-present	Professor, Department of Life Science, University of Seoul, South Korea
	2012-2017	Associate Professor, Department of Life Science, University of Seoul, South Korea
	2008-2012	Assistant Professor, Department of Life Science, University of Seoul, South Korea
	2005-2008	Research Associate, Department of Biological Sciences, Stanford University, USA
	2001-2005	Post-doctoral Research Fellow, Department of Biological Sciences, Stanford University, USA
	1995-2001	PhD, Ohio State Biochemistry Program, The Ohio State University, USA
	1992-1994	MS, Department of Chemistry, Seoul National University, South Korea
	1987-1992	BS, Department of Chemistry, Seoul National University, South Korea

Lipocalin-2: a therapeutic target to overcome neurodegenerative diseases by regulating reactive astrogliosis

Glial cell activation precedes neuronal cell death during brain aging and the progression of neurodegenerative diseases. Under neuroinflammatory stress conditions, lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin or 24p3, is produced and secreted by activated microglia and reactive astrocytes. Lcn2 expression levels are known to be increased in various cells, including reactive astrocytes, through the activation of the NF-κB signaling pathway. In the central nervous system, as LCN2 exerts neurotoxicity when secreted from reactive astrocytes, many researchers have attempted to identify various strategies to inhibit LCN2 production, secretion, and function to minimize neuroinflammation and neuronal cell death. These strategies include regulation at the transcriptional, posttranscriptional, and posttranslational levels, as well as blocking its functions using neutralizing antibodies or antagonists of its receptor. The suppression of NF-κB signaling is a strategy to inhibit LCN2 production, but it may also affect other cellular activities, raising questions about its effectiveness and feasibility. Recently, LCN2 was found to be a target of the autophagy‒lysosome pathway. Therefore, autophagy activation may be a promising therapeutic strategy to reduce the levels of secreted LCN2 and overcome neurodegenerative diseases. In this review, we focused on research progress on astrocyte-derived LCN2 in the central nervous system.

Exp Mol Med. 2023 Oct 2;55(10):2138‒2146. doi: 10.1038/s12276-023-01098-7.
https://www.ncbi.nlm.nih.gov/pubmed/37779143