Dataset Information

Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair.

ABSTRACT: : Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs undergo profound changes in their morphology, functions, and interactions with other cells and extracellular environment, thus requiring the reorganization of both their lipid metabolism and their membrane composition, which is substantially different compared to other plasma membranes. Despite the growing knowledge in oligodendroglia biology and in the mechanisms involved in OPC-mediated regeneration, the identification of strategies to promote remyelination still remains a challenge. Here, we describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and we show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.

SUBMITTER: Marangon D

PROVIDER: S-EPMC7073561 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair.

Marangon Davide D Boccazzi Marta M Lecca Davide D Fumagalli Marta M

Journal of clinical medicine 20200208 2

<b>:</b> Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs unde ...[more]

PMID: 32046349

Similar Datasets

Project description:Oligodendrocytes are the glial cells responsible for the formation of the myelin sheath around axons. During neurodevelopment, oligodendrocytes undergo maturation and differentiation, and later remyelination in adulthood. Abnormalities in these processes have been associated with behavioral and cognitive dysfunctions and the development of various mental illnesses like schizophrenia. Several studies have implicated oligodendrocyte dysfunction and myelin abnormalities in the disorder, together with altered expression of myelin-related genes such as Olig2, CNP, and NRG1. However, the molecular mechanisms subjacent of these alterations remain elusive. Schizophrenia is a severe, chronic psychiatric disorder affecting more than 23 million individuals worldwide and its symptoms usually appear at the beginning of adulthood. Currently, the major therapeutic strategy for schizophrenia relies on the use of antipsychotics. Despite their widespread use, the effects of antipsychotics on glial cells, especially oligodendrocytes, remain unclear. Thus, in this review we highlight the current knowledge regarding oligodendrocyte dysfunction in schizophrenia, compiling data from (epi)genetic studies and up-to-date models to investigate the role of oligodendrocytes in the disorder. In addition, we examined potential targets currently investigated for the improvement of schizophrenia symptoms. Research in this area has been investigating potential beneficial compounds, including the D-amino acids D-aspartate and D-serine, that act as NMDA receptor agonists, modulating the glutamatergic signaling; the antioxidant N-acetylcysteine, a precursor in the synthesis of glutathione, protecting against the redox imbalance; as well as lithium, an inhibitor of glycogen synthase kinase 3? (GSK3?) signaling, contributing to oligodendrocyte survival and functioning. In conclusion, there is strong evidence linking oligodendrocyte dysfunction to the development of schizophrenia. Hence, a better understanding of oligodendrocyte differentiation, as well as the effects of antipsychotic medication in these cells, could have potential implications for understanding the development of schizophrenia and finding new targets for drug development.

Dataset Information

Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair.

Publications

Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets