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.
Regulation of oligodendrocyte functions : targeting lipid metabolism and extracellular matrix for myelin repair / D. Marangon, M. Boccazzi, D. Lecca, M. Fumagalli. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - 9:2(2020 Feb 08), pp. 470.1-470.22.
|Titolo:||Regulation of oligodendrocyte functions : targeting lipid metabolism and extracellular matrix for myelin repair|
MARANGON, DAVIDE (Primo)
BOCCAZZI, MARTA (Secondo)
LECCA, DAVIDE (Penultimo)
FUMAGALLI, MARTA (Ultimo) (Corresponding)
|Parole Chiave:||extracellular matrix; lipid metabolism; myelin; remyelination|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Progetto:||New strategies to enhance the trophic functions and remyelinating abilities of adult NG2-glia in amyotrophic lateral sclerosis via the GPR17 receptor (GPR17ALS-1)|
Effects of microglia-derived vesicles on GPR17-expressing oligodendrocyte precursors and remyelination after brain ischemia: new molecular insights and recovery potential
Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI
|Data di pubblicazione:||8-feb-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/jcm9020470|
|Appare nelle tipologie:||01 - Articolo su periodico|