Biomaterial Database

Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation. 2022

Tess Dierckx, and Sam Vanherle, and Mansour Haidar, and Elien Grajchen, and Fleur Mingneau, and Pascal Gervois, and Esther Wolfs, and Dany Bylemans, and Arnout Voet, and Tien Nguyen, and Ibrahim Hamad, and Markus Kleinewietfeld, and Jeroen F J Bogie, and Jerome J A Hendriks

Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek 3590, Belgium.

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequently fail in these disorders is poorly understood. However, there is now evidence indicating that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Previously, we found that phloretin, a flavonoid abundantly present in apples and strawberries, reduces neuroinflammation by driving macrophages toward an antiinflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animal models. Improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred independently from alterations in microglia function and inflammation. We found, mechanistically, that phloretin acts as a direct ligand for the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma, thereby promoting the maturation of OPCs. Together, our findings indicate that phloretin has proregenerative properties in central nervous system disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions aimed at promoting remyelination.

UI	MeSH Term	Description	Entries
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009186	Myelin Sheath	The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.	Myelin,Myelin Sheaths,Sheath, Myelin,Sheaths, Myelin
D009836	Oligodendroglia	A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.	Interfascicular Oligodendroglia,Oligodendrocytes,Perineuronal Oligodendroglia,Perineuronal Satellite Oligodendroglia Cells,Perivascular Oligodendroglia,Satellite Cells, Perineuronal, Oligodendroglia,Perineuronal Satellite Oligodendrocytes,Interfascicular Oligodendroglias,Oligodendrocyte,Oligodendrocyte, Perineuronal Satellite,Oligodendrocytes, Perineuronal Satellite,Oligodendroglia, Interfascicular,Oligodendroglia, Perineuronal,Oligodendroglia, Perivascular,Perineuronal Satellite Oligodendrocyte,Satellite Oligodendrocyte, Perineuronal,Satellite Oligodendrocytes, Perineuronal
D010693	Phloretin	A natural dihydrochalcone found in apples and many other fruits.
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D000073637	Oligodendrocyte Precursor Cells	Neuroglial cells that first appear during mid-embryogenesis in the central nervous system of mammals and give rise to OLIGODENDROCYTES. Mitotically-active populations remain through late adulthood and are capable of regenerating MYELIN lost to disease or injury.	Oligodendrocyte Precursors,Oligodendrocyte Progenitor Cells,Oligodendrocyte Progenitors,Pre-Oligodendrocytes,Preoligodendrocytes,Cell, Oligodendrocyte Precursor,Cell, Oligodendrocyte Progenitor,Cells, Oligodendrocyte Precursor,Cells, Oligodendrocyte Progenitor,Oligodendrocyte Precursor,Oligodendrocyte Precursor Cell,Oligodendrocyte Progenitor,Oligodendrocyte Progenitor Cell,Pre Oligodendrocytes,Pre-Oligodendrocyte,Precursor Cell, Oligodendrocyte,Precursor Cells, Oligodendrocyte,Precursor, Oligodendrocyte,Precursors, Oligodendrocyte,Preoligodendrocyte,Progenitor Cell, Oligodendrocyte,Progenitor Cells, Oligodendrocyte,Progenitor, Oligodendrocyte,Progenitors, Oligodendrocyte
D000074586	Remyelination	The reforming of the MYELIN SHEATH around AXONS following loss due to injury or DEMYELINATING DISEASES.	Remyelinations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus