KDM1A/LSD1 as a promising target in various diseases treatment by regulating autophagy network

Abstract

Epigenetics refers to alterations in gene expressions that are reversible and stable, but do not involve changes in DNA sequences. In recent years, an increasing number of studies have shown that epigenetics plays a critical role in autophagy, which can be schematized as a biological process comprising of the following steps: autophagy signal activation, autophagic vesicle elongation, autophagosome maturation and autophagosome-lysosome fusion. As previously reported, autophagy can maintain intracellular homeostasis and autophagy dysfunction will lead to various diseases. For instance, the abnormal expression of genes involved in autophagy can result in the occurrence of many cancers and atherosclerosis. It is also well known that epigenetic modifications can affect autophagy related genes expressions and modulate other signaling molecular involved in autophagy. As an important epigenetic enzyme, LSD1 (lysine specific demethylase 1) plays an essential role in modulating autophagy. On one hand, LSD1 directly regulates autophagy-related genes expressions, including ATGs, Beclin-1, LC3 and SQSTM1/p62. On the other hand, inhibition of LSD1 can activate autophagy through regulating the activities of some other proteins such as p53, SESN2, mTORC1 and PTEN. Since autophagy activation is tightly related to the occurrence of various diseases and can be induced by LSD1 inhibition, development of LSD1 inhibitors will provide a new direction to treat such diseases. In this review, we described the mechanisms by which LSD1 regulates autophagy in different manners and how autophagic dysfunction leads to diseases occurrence. In addition, some LSD1 inhibitors used to treat diseases through modulating autophagy are also summarized in our review.

Keywords: Autophagy; Diseases; Inhibitors; LSD1.