The role of cholesterol during remyelination for multiple sclerosis: advances in metabolic regulation, potential therapeutic targets, <?A3B2 pi6?>and drug research

<p indent="0mm">Myelin damage in central nervous system demyelinating diseases severely disrupts white matter function and can even lead to gray matter injury. The disease can result in neurodegenerative changes and functional disability, which cause a significant burden on individuals and society. Currently, the treatment of central nervous system demyelinating diseases mainly focuses on anti-inflammatory effects to reduce demyelination. Most of them have not achieved repair of already damaged myelin, making it difficult to recover patient function further. Although inflammatory damage to myelin debris is a common pathological feature of central nervous system demyelinating diseases, myelin repair also should not be overlooked. How to promote remyelination and achieve functional recovery have aroused the interest of many researchers. It has gradually become a core therapeutic goal for central nervous system demyelinating diseases represented by multiple sclerosis (MS). In recent years, the important role of cholesterol on remyelination has been a concern. Firstly, cholesterol can serve as a fundamental substance for promoting remyelination. Secondly, synthetic precursors and major metabolites of cholesterol can also facilitate remyelination by improving differentiation of oligodendrocyte progenitor cells (OPCs). However, the origin of cholesterol in the brain is relatively straightforward, with its primary sources being <italic>de novo</italic> synthesis and the recycling of cholesterol. Related drugs primarily target these two pathways. Through literature mining, this review summarizes the mechanisms of cholesterol supply and the role of cholesterol during remyelination and sorts out potential targets and drugs to promote remyelination. This study is helpful in exploring the potential value of cholesterol during remyelination, and provides references for the screening of innovative drugs for remyelination from cholesterol metabolism.