Central Regulation of Osteocalcin and Its Biological Mechanism / 中国生物化学与分子生物学报

ABSTRACT

Osteocalcin (OCN) regulates the physiological structure and function of various peripheral tissues and organs, and plays a central regulatory role, which is tightly associated with higher-level cognitive functions such as learning and memory. Studies have shown that OCN can enter the central nervous system through the blood-brain barrier and bind to GPR158 and GPR37, members of the G protein-coupled receptor (GPCR) family on the membrane of neurons or glial cells, activate or inhibit relevant intracellular signalling pathways, and then change the physiological activities of neurons or glial cells. In the brain, the role of OCN mainly includes regulating the synthesis and release of neurotransmitters such as serotonin, dopamine, norepinephrine and γ-aminobutyric acid, increasing the expression of brain-derived neurotrophic factor, promoting hippocampal neurogenesis, enhancing hippocampal neuron autophagy and maintaining myelin homeostasis, among others. Furthermore, OCN can also be involved in the regulation of the pathophysiological process of multiple neurodegenerative diseases. In Alzheimer's disease (AD), OCN treatment reduces β-amyloid protein (Aβ) deposition and Aβ-induced cytotoxicity in part, thereby improving learning and memory deficits; in Parkinson's disease (PD), OCN treatment inhibits the loss of substantia nigra and striatum dopaminergic neurons, increases the content of tyrosine hydroxylase and decreases neuroinflammation, thereby alleviating motor dysfunction. By analyzing the structure and function of GPR158 and GPR37, analyzing the role of OCN in the brain and its biological mechanism, and exploring the effect of OCN on neurodegenerative diseases such as AD and PD, this paper aims to provide a basis for further screening new targets to promote brain health.