Abstract
Oligodendrocytes (OLs) are the myelinating cells of the central nervous system (CNS) during development and throughout adulthood. They result from a complex and well controlled process of activation, proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs) from the germinative niches of the CNS. In multiple sclerosis (MS), the complex pathological process produces dysfunction and apoptosis of OLs leading to demyelination and neurodegeneration. This review attempts to describe the patterns of demyelination in MS, the steps involved in oligodendrogenesis and myelination in healthy CNS, the different pathways leading to OLs and myelin loss in MS, as well as principles involved in restoration of myelin sheaths. Environmental factors and their impact on OLs and pathological mechanisms of MS are also discussed. Finally, we will present evidence about the potential therapeutic targets in re-myelination processes that can be accessed in order to develop regenerative therapies for MS.
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Abbreviations
- BBB:
-
blood-brain barrier
- CIS:
-
clinically isolated syndrome
- CNS:
-
central nervous system
- CSF:
-
cerebrospinal fluid
- DIR:
-
double inversion recovery
- DMF:
-
Dimethyl Fumarate
- DTI:
-
diffusion tensor imaging
- EAE:
-
experimental autoimmune encephalomyelitis
- GA:
-
glatiramer acetate
- Gd:
-
gadolinium
- GM:
-
gray matter
- HERV:
-
human endogenous retroviruses
- MAG:
-
myelin associated glycoprotein
- MBP:
-
myelin basic protein
- MMPs:
-
matrix metalloproteinases
- LQ:
-
laquinimod
- MOG:
-
myelin oligodendrocyte glycoprotein
- 3D-MPRAGE:
-
3-dimensional magnetization prepared acquisition with gradient-echo
- MRI:
-
magnetic resonance imaging
- MS:
-
multiple sclerosis
- MSRV:
-
multiple sclerosis associated retrovirus
- MTR:
-
magnetization transfer ratio
- NAWM:
-
normal appearing white matter
- OL:
-
oligodendrocyte
- omGP:
-
oligodendrocyte myelin glycoprotein
- OPC:
-
oligodendrocyte progenitor cell
- OSP:
-
oligodendrocyte surface protein
- PLP:
-
proteolipid protein
- PPMS:
-
primary progressive multiple sclerosis
- PSIR:
-
phase sensitive inversion recovery
- rHIgM22:
-
human monoclonal IgM antibody 22
- RRMS:
-
relapsing remitting multiple sclerosis
- SPMS:
-
secondary progressive multiple sclerosis
- TNF-α:
-
tumor necrosis factor-alpha
- USPIO:
-
ultra-small superparamagnetic particles of iron oxide
- WM:
-
white matter
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The author thanks to the staff of Neurology Clinic of Fundeni Clinical Institute and University of Medicine and Pharmacy “Carol Davila” Bucharest.
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Dulamea, A.O. (2017). Role of Oligodendrocyte Dysfunction in Demyelination, Remyelination and Neurodegeneration in Multiple Sclerosis. In: Asea, A., Geraci, F., Kaur, P. (eds) Multiple Sclerosis: Bench to Bedside. Advances in Experimental Medicine and Biology, vol 958. Springer, Cham. https://doi.org/10.1007/978-3-319-47861-6_7
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