New insights into LSD1: a key regulator in disease pathogenesis

A new review highlights the pivotal role of LSD1 (lysine-specific demethylase 1) in regulating critical cellular processes and its implications for human diseases. This article sheds light on how post-translational modifications (PTMs) influence LSD1 activity, impacting its function in gene regulation and disease progression.

LSD1 is a histone demethylase that plays a significant role in chromatin remodeling and gene expression by modifying histone H3 lysine residues. It interacts with various protein complexes, allowing it to serve as both a transcriptional activator and repressor. The intricate modifications of LSD1, including phosphorylation, acetylation, ubiquitination, methylation, SUMOylation, and S-nitrosylation, dictate its enzymatic activity, subcellular localization, and stability. The disruption of these modifications has been linked to multiple pathological conditions, including cancer, metabolic disorders, neurological diseases, cardiovascular conditions, and bone disorders.

The overexpression of LSD1 has been observed in various tumors, where it facilitates the suppression of tumor suppressor genes and promotes cancer cell proliferation. LSD1’s interaction with oncogenic pathways contributes to tumorigenesis and metastasis, making it a promising therapeutic target. In metabolic diseases, LSD1 has been implicated in adipose tissue differentiation and insulin sensitivity, suggesting potential strategies for obesity and diabetes management. Furthermore, LSD1 is crucial in neurodevelopment, with dysregulation linked to autism, Alzheimer’s disease, and amyotrophic lateral sclerosis.

The growing body of evidence on LSD1’s role in gene expression and disease mechanisms opens new avenues for targeted therapy. Inhibitors of LSD1 are currently being explored as potential treatments for cancer and neurological disorders, aiming to restore normal cellular function by modulating its activity. The findings presented in this review reinforce the significance of post-translational modifications as regulatory mechanisms and underscore the need for further research into precision medicine approaches targeting LSD1.

By expanding our understanding of LSD1 and its modifications, this research provides a foundation for developing novel therapeutic strategies, offering hope for improved treatments across a range of diseases linked to LSD1 dysfunction.

 

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Reference

Yinrui Li, Bo Wang, Yichao Zheng, Huiqin Kang, Ang He, Lijuan Zhao, Ningjie Guo, Hongmin Liu, Adil Mardinoglu, M.A.A. Mamun, Ya Gao, Xiaobing Chen, The multifaceted role of post-translational modifications of LSD1 in cellular processes and disease pathogenesis, Genes & Diseases, Volume 12, Issue 3, 2025, 101307, https://doi.org/10.1016/j.gendis.2024.101307

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