NG2-Positive Oligodendrocyte Progenitor Cells in Adult Human Brain and Multiple Sclerosis Lesions

Chang, Ansi; Nishiyama, Akiko; Peterson, John W.; Prineas, John W.; Trapp, Bruce D.

doi:10.1523/jneurosci.20-17-06404.2000

Cited by 659 publications

(559 citation statements)

References 41 publications

(49 reference statements)

Supporting

Mentioning

516

Contrasting

Unclassified

Order By: Relevance

“…OPCs are indispensable during oligodendrocyte differentiation and myelin remyelination; they are activated for remyelination in MS lesions [85,86] . They also play an important role in MS pathogenesis by modulating immune activity in the CNS.…”

Section: Autophagy In Glial Cellsmentioning

confidence: 99%

“…mTOR in the astrocyte may play a protective role in ischemia via its downstream kinase S6K1 [81] . mTOR can also regulate the stability of iNOS mRNA in astrocytes, reducing the neurotoxic effect of NO which impairs autophagy by disrupting the BECN1 complex and activates mTORC1 [82][83][84] .OPCs are indispensable during oligodendrocyte differentiation and myelin remyelination; they are activated for remyelination in MS lesions [85,86] . They also play an important role in MS pathogenesis by modulating immune activity in the CNS.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Role of autophagy in the pathogenesis of multiple sclerosis

Liang

2015

Neurosci. Bull.

View full text Add to dashboard Cite

Autophagy plays an important role in maintaining the cellular homeostasis. One of its functions is to degrade unnecessary organelles and proteins for energy recycling or amino-acids for cell survival. Ablation of autophagy leads to neurodegeneration. Multiple sclerosis (MS), a permanent neurological impairment typical of chronic inflammatory demyelinating disorder, is an auto-immune disease of the central nervous system (CNS). Autophagy is tightly linked to the innate and adaptive immune systems during the autoimmune process, and several studies have shown that autophagy directly participates in the progress of MS or experimental autoimmune encephalomyelitis (EAE, a mouse model of MS). Dysfunction of mitochondria that intensively infl uences the autophagy pathway is one of the important factors in the pathogenesis of MS. Autophagy-related gene (ATG) 5 and immune-related GTPase M (IRGM) 1 are increased, while ATG16L2 is decreased, in T-cells in EAE and active relapsing-remitting MS brains. Administration of rapamycin, an inhibitor of mammalian target of rapamycin ( mTOR), ameliorates relapsing-remitting EAE. Infl ammation and oxidative stress are increased in MS lesions and EAE, but Lamp2 and the LC3-II/LC3-I ratio are decreased. Furthermore, autophagy in various glial cells plays important roles in regulating neuro-infl ammation in the CNS, implying potential roles in MS. In this review, we discuss the role of autophagy in the peripheral immune system and the CNS in neuroinfl ammation associated with the pathogenesis of MS. Keywords: autophagy; multiple sclerosis; neuro-infl ammation ·Review· IntroductionAutophagy, a lysosome-dependent degradation pathway, contributes to maintaining cellular homeostasis. Clearance of long-lived proteins, unnecessary organelles, and aggregate-prone proteins is mainly executed by autophagy for recycling cellular materials [1] . There are three subtypes of autophagy, macroautophagy, chaperone-mediated autophagy (CMA), and mitophagy. Macroautophagy is the major type for selective degradation of protein aggregates or misfolded proteins. The ubiquitin-labeled proteins are recognized by autophagy receptors, such as p62, neighbor of BRCA1 gene 1 (NBR1), and NIP3-like protein X (NIX), to form autophagosomes that then fuse with lysosomes for degradation. Many autophagy-related genes function during this process, such as Unc51-like kinase (ULK1) and autophagy-related gene (ATG) 5. Mammalian target of rapamycin (mTOR) represses autophagy by regulating ULK1 phosphorylation, while AMPK activates this process.CMA mediates the degradation of large molecular-weight proteins containing the KFERQ motif recognized by heat shock cognate protein of 70 kDa (HSC70). The substrate is then escorted to lysosome-associated membrane protein 2 (LAMP2A) for lysosomal degradation. Mitophagy is responsible for the degradation of damaged mitochondria.Parkin and PINK1 play critical roles in this process [2] . More Neurosci Bull August 1, 2015, 31(4): 435-444 436 attention has been paid to autophagy in the path...

show abstract

Section: Autophagy In Glial Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

Role of autophagy in the pathogenesis of multiple sclerosis

Liang

2015

Neurosci. Bull.

View full text Add to dashboard Cite

show abstract

“…Some studies showed a depletion of progenitor cells after focal demyelination in experimental animals [52,74], whereas others showed that repeated episodes of demyelination did not slow down remyelination [75]. In pathological specimens of chronic MS lesions in human patients, neither decrease nor reactive increase was observed relative to normal white matter [39,[76][77][78]. This suggests that the response of the progenitor cell population to the demyelinating process in the human brain is deficient.…”

Section: Myelin Regeneration Fails In Msmentioning

confidence: 99%

“…Alternatively, if reversible cell autonomous factors or inhibitory factors that are expressed in the demyelinated tissue limit OPC differentiation into remyelinating oligodendrocytes, then the rationale treatment would be to target them directly. Active inhibition of resident OPCs is suggested by the sharp border of demyelinated plaque, surrounded by OPCs [39,76,77]. It was suggested, for example, that re-expression of Notch1, a regulator of oligodendrocyte progenitor differentiation, inhibits remyelination in MS [85].…”

Section: Myelin Regeneration Fails In Msmentioning

confidence: 99%

Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

View full text Add to dashboard Cite

The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

show abstract

“…18 However, in chronic MS, remyelination fails and axonal function is irreversibly compromised, despite the presence of OPCs within lesions. 19 …”

Section: Oligodendrocytes and Axoglial Interactionsmentioning

confidence: 99%

Functions of optic nerve glia: axoglial signalling in physiology and pathology

Butt

Pugh

Hubbard

et al. 2004

Eye

View full text Add to dashboard Cite

An early concept of glial function envisaged them as passive and unexcitable structural elements, much like the connective tissues of organs in the periphery. It is now known that glia have a widespread range of physiological roles and react to all forms of pathological insult. This paper reviews the major functions of oligodendrocytes and astrocytes, the main types of glia in the optic nerve, and examines novel NG2-glia, otherwise known as oligodendrocyte progenitor cells (OPCs). The major function of oligodendrocytes is to produce the myelin sheaths that insulate CNS axons, but they also have important roles in the establishment of nodes of Ranvier, the sites of action potential propagation, and axonal integrity. Astrocytes have multiple physiological and pathological functions, including potassium homeostasis and metabolism, and reactive astrogliosis in response to CNS insults. The bulk of NG2-glia are postmitotic complex cells, distinct from OPCs, and respond to any insult to the CNS by a rapid and stereotypic injury response. This may be their primary unction, but NG2-glia, or a subpopulation of NG2-expressing adult OPCs, also provide remyelinating oligodendrocytes following demyelination. Oligodendrocytes, astrocytes, and NG2-glia all contact axons at nodes of Ranvier and respond to glutamate, ATP, and potassium released during axonal electrical activity. Glutamate and ATP evoke calcium signalling in optic nerve glia and have dual roles in physiology and pathology, coupling glial functions to axonal activity during normal activity, but enhanced activation induces an injury response, as seen following injury, demyelination, and ischaemia.

show abstract

NG2-Positive Oligodendrocyte Progenitor Cells in Adult Human Brain and Multiple Sclerosis Lesions

Cited by 659 publications

References 41 publications

Role of autophagy in the pathogenesis of multiple sclerosis

Role of autophagy in the pathogenesis of multiple sclerosis

Cell Therapy for Multiple Sclerosis

Functions of optic nerve glia: axoglial signalling in physiology and pathology

Contact Info

Product

Resources

About