Review
Clinical Neurology
Vanja Tepavcevi, Catherine Lubetzki
Summary: The failure of remyelination in multiple sclerosis (MS) is often characterized by low oligodendrocyte progenitor cell density. Stimulating this process may be crucial for achieving myelin regeneration.
Article
Chemistry, Multidisciplinary
Shi-hao Cui, Na Suo, Ying Yang, Xuan Wu, Shi-meng Guo, Xin Xie
Summary: Oligodendrocytes (OLs), glial cells in the central nervous system, are responsible for forming myelin. It has been found that compounds U73122 and U73343 promote the differentiation of OLs and myelin regeneration by regulating the cholesterol biosynthesis pathway.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Multidisciplinary Sciences
Khalil S. S. Rawji, Bjorn Neumann, Robin J. M. Franklin
Summary: Aging has significant effects on the functional phenotype of glial cells, leading to an inflammatory microenvironment and increased risk of neuron and synapse loss. Additionally, aging glial cells have negative implications for central nervous system remyelination.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Review
Cell Biology
Federica Cherchi, Anna Maria Pugliese, Elisabetta Coppi
Summary: Oligodendrocyte-formed myelin sheaths facilitate fast synaptic transmission in the brain, but their degeneration can lead to demyelinating diseases. Remyelination relies on the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes, with the neuromodulator adenosine and its receptors playing crucial roles in this process. The review highlights the potential therapeutic targets in demyelinating pathologies like multiple sclerosis by targeting adenosine receptor ligands.
NEURAL REGENERATION RESEARCH
(2021)
Review
Neurosciences
Mohanlall Narine, Holly Colognato
Summary: Oligodendroglial cells play important roles in neurological functions such as myelination, neuroprotection, and motor learning. Recent studies have focused on understanding the role of oligodendroglial metabolism in regulating cell development, energy supply to neighboring cells, and its contribution to disease states. Inputs such as cellular signaling, pharmacological compounds, and dietary interventions can regulate oligodendroglial metabolism. Targeting components within oligodendroglial bioenergetic pathways may have therapeutic potential.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Civia Z. Chen, Bjorn Neumann, Sarah Forster, Robin J. M. Franklin
Summary: Myelin sheaths are crucial for neuronal function by supporting axonal integrity and rapid impulse conduction. In response to demyelinating injuries in the CNS, OPCs can undergo remyelination. OPCs might be a major source of CNS-resident SCs, which could be an attractive target for promoting endogenous remyelination.
Article
Neurosciences
James J. M. Cooper, Jessie J. Polanco, Darpan Saraswat, Jennifer J. Peirick, Anna Seidl, Yi Li, Dan Ma, Fraser J. Sim
Summary: The failure of remyelination in the human CNS is a major contributor to axonal injury and disease progression in multiple sclerosis (MS). Murine models show a high density of oligodendrocyte progenitor cells (OPCs) in areas of demyelination, suggesting that efficient OPC repopulation is necessary for successful remyelination. However, in this study, we found that OPC repopulation was low in large lesions and almost absent in small lesions in adult rabbits, suggesting that both lesion volume and species-specific mechanisms play a role in regulating OPC proliferation and remyelination.
Article
Neurosciences
Melanie Piller, Inge L. Werkman, Evan A. Brown, Andrew J. Latimer, Sarah Kucenas
Summary: The study found that the ionotropic glutamate receptor subunit GluR4A plays a crucial role in OPC migration and myelination, disruption of which leads to abnormal migration and distribution of OPCs in the spinal cord. Through genetic and pharmacological experiments, it was discovered that voltage-gated calcium channels are downstream of glutamate receptor signaling in OPCs and can rescue migration and myelination defects caused by disrupted glutamate signaling.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Jiayue Hong, Julia M. Kirkland, Jenica Acheta, Leandro N. Marziali, Brianna Beck, Haley Jeanette, Urja Bhatia, Grace Davis, Jacob Herron, Clemence Roue, Charly Abi-Ghanem, M. Laura Feltri, Kristen L. Zuloaga, Marie E. Bechler, Yannick Poitelon, Sophie Belin
Summary: In this study, the importance of YAP and TAZ in oligodendrocyte function was investigated. Deletion of these mechanotransducers in adult oligodendroglial cells did not affect animal viability or OL maturation and myelination. However, YAP and TAZ were found to play a critical role in the capacity of OLs to remyelinate axons, particularly during the early stage of repair.
Review
Neurosciences
Lauren Rose Hirschfeld, Shannon L. Risacher, Kwangsik Nho, Andrew J. Saykin
Summary: This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease, and discusses therapeutic targets and potential research directions.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Cell Biology
Andrea D. Rivera, Francesca Pieropan, Irene Chacon-De-La-Rocha, Davide Lecca, Maria P. Abbracchio, Kasum Azim, Arthur M. Butt
Summary: Brain ageing is characterized by a decline in neuronal function and cognitive deficits, with myelin disruption being identified as a significant factor contributing to the loss of brain plasticity and repair responses. Through a combined systems biology and neurobiological approach, it was found that oligodendroglial and myelin genes are highly altered in the aging mouse cerebrum, with the G-protein coupled receptor Gpr17 being central to the disruption of OPCs in aging. Systems biology strategies were used to identify therapeutic agents that rejuvenate OPCs and restore myelination in age-related neuropathological contexts.
Article
Neurosciences
Darpan Saraswat, R. Ross Welliver, Roopa Ravichandar, Ajai Tripathi, Jessie J. Polanco, Jacqueline Broome, Edward Hurley, Ranjan Dutta, M. Laura Feltri, Fraser J. Sim
Summary: IFN-gamma, a proinflammatory cytokine elevated in multiple sclerosis, induces pathologic quiescence in human oligodendrocyte progenitor cells via upregulation of the transcription factor PRRX1. Heparan sulfate proteoglycans play a key role in modulating IFN-gamma signaling following demyelination, and its modulation can mitigate the negative effects of proinflammatory signaling in the inflamed and demyelinated human brain.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Jacob H. Hines
Summary: Oligodendrocytes are essential for neural function in gnathostomes, with well-established roles in myelination, but recent studies have shown their involvement in other aspects of central nervous system development, function, and maintenance. Advances in understanding myelin plasticity have revealed experience-dependent adaptations as a form of neural plasticity. The evolutionary origins and specializations of oligodendrocytes remain mysteries, prompting questions about when and for what functions the cell type emerged, and the genetic changes responsible for their evolutionary innovations.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Tess Dierckx, Sam Vanherle, Mansour Haidar, Elien Grajchen, Fleur Mingneau, Pascal Gervois, Esther Wolfs, Dany Bylemans, Arnout Voet, Tien Nguyen, Ibrahim Hamad, Markus Kleinewietfeld, Jeroen F. J. Bogie, Jerome J. A. Hendriks
Summary: This study reveals the reasons for the failure of remyelination, including the overly inflammatory microenvironment and the intrinsic inability of oligodendrocyte precursor cells to differentiate. The study also shows that phloretin can significantly promote remyelination by acting on the nuclear receptor peroxisome proliferator-activated receptor gamma to promote the maturation of oligodendrocyte precursor cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Carlie L. Cullen, Megan O'Rourke, Shannon J. Beasley, Loic Auderset, Yilan Zhen, Renee E. Pepper, Robert Gasperini, Kaylene M. Young
Summary: Primary cilia play a crucial role in the myelination process of oligodendrocyte progenitor cells, with their assembly regulated by the gene Kif3a. Deletion of Kif3a leads to decreased OPC proliferation and oligodendrogenesis, affecting fine motor coordination in specific brain regions.
Article
Neurosciences
Na Suo, Yu-e Guo, Bingqing He, Haifeng Gu, Xin Xie
Article
Multidisciplinary Sciences
Yue Wang, Shimeng Guo, Youwen Zhuang, Ying Yun, Peiyu Xu, Xinheng He, Jia Guo, Wanchao Yin, H. Eric Xu, Xin Xie, Yi Jiang
Summary: Ghrelin, a gastric peptide hormone, requires acylation for binding and activation of the ghrelin receptor in the brain to initiate appetite. The cryo-EM structures of the G(q)-coupled ghrelin receptor bound to ghrelin and the synthetic agonist GHRP-6 provide insights into how the acylated peptide hormone is recognized by the receptor, which is important for drug design.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Shimeng Guo, Tingting Zhao, Ying Yun, Xin Xie
Summary: G-protein-coupled receptors (GPCRs), the largest family of cell surface receptors in eukaryotes, are involved in regulating various physiological processes. Targeting GPCRs with drugs is a major focus in drug discovery research, but the complex signaling mechanisms of GPCRs, involving protein-protein interactions, have posed challenges. Recent advancements in protein-protein interaction detection technologies, such as fluorescence resonance energy transfer/bioluminescence resonance energy transfer (FRET/BRET) and NanoLuc binary technology (NanoBiT), have been applied to study the interactions between GPCRs and signaling partners. Furthermore, when using animal models to study the in vivo functions of GPCR ligands, species differences in GPCRs can be addressed using modern genetic tools.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Neurosciences
Na Suo, Bingqing He, Shihao Cui, Ying Yang, Min Wang, Qianting Yuan, Xin Xie
Summary: GPR149, an orphan G protein-coupled receptor enriched in OPCs, negatively regulates OPC to OL differentiation and myelination, impacting myelin development and remyelination. Deficiency of GPR149 enhances myelin regeneration. Further study suggests that GPR149 may regulate OL differentiation and myelin formation via the MAPK/ERK pathway.
Article
Gastroenterology & Hepatology
Mengmeng Jiang, Ren Guo, Yan Ai, Gang Wang, Peilan Tang, Xiaohui Jia, Bingqing He, Qianting Yuan, Xin Xie
Summary: Hepatocyte transplantation is a potential treatment for end-stage liver disease, but low engraftment and proliferation of transplanted hepatocytes hinder therapeutic success. This study aimed to investigate the mechanisms of hepatocyte proliferation in vivo and identify compounds that promote the growth of transplanted hepatocytes.
Article
Biochemistry & Molecular Biology
Sijia Ji, Wanzhi Tu, Chenwen Huang, Ziyang Chen, Xinyue Ren, Bingqing He, Xiaoyan Ding, Yuelei Chen, Xin Xie
Summary: This study reveals that the Aurora kinase inhibitor CYC116 significantly promotes the maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). It increases the expression of genes related to cardiomyocyte function, improves the organization of sarcomeres, increases the number of mitochondria, and enhances the physiological function of the cells.
MOLECULES AND CELLS
(2022)
