Physiological and pathological effects of phase separation in the central nervous system

Phase separation, also known as biomolecule condensate, participates in physiological processes such as transcriptional regulation, signal transduction, gene expression, and DNA damage repair by creating a membrane-free compartment. Phase separation is primarily caused by the interaction of multivalent non-covalent bonds between proteins and/or nucleic acids. The strength of molecular multivalent interaction can be modified by component concentration, the potential of hydrogen, posttranslational modification, and other factors. Notably, phase separation occurs frequently in the cytoplasm of mitochondria, the nucleus, and synapses. Phase separation in vivo is dynamic or stable in the normal physiological state, while abnormal phase separation will lead to the formation of biomolecule condensates, speeding up the disease progression. To provide candidate suggestions for the clinical treatment of nervous system diseases, this review, based on existing studies, carefully and systematically represents the physiological roles of phase separation in the central nervous system and its pathological mechanism in neurodegenerative diseases.