Role of Lipocalin-2 in Amyotrophic Lateral Sclerosis

Zhuoya Wang¹Wen Cao¹Dongsheng Fan^1,2,3*

• ¹Peking University Third Hospital, Haidian, China
• ²Beijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China
• ³Key Laboratory for Neuroscience, National Health Commission/Ministry of Education, Beijing, China

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized pathologically by degeneration of upper and lower motor neurons, ultimately leading to muscle weakness and respiratory failure. Lipocalin-2 (LCN2) is a secreted protein involved in lipid transport that plays a key role in inflammatory responses and the regulation of iron homeostasis. The role of LCN2 in ALS has attracted increasing attention, as significantly elevated LCN2 expression has been observed in the blood and postmortem tissues of ALS patients. Functionally, LCN2 participates in neuroinflammation, iron dysregulation, cell death, and peripheral immune immunity, proposing a central-peripheral linkage hypothesis mediated by LCN2. Clinically, LCN2 shows promise as both a biomarker and a therapeutic target, with multiple strategies demonstrating potential to mitigate ALS pathology. Moving forward, it is essential to integrate multi-omics to deeply decipher LCN2-mediated molecular networks, advance patient stratification, and accelerate its clinical translation.