2020
DOI: 10.1002/jnr.24582
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Remodeling of the interstitial extracellular matrix in white matter multiple sclerosis lesions: Implications for remyelination (failure)

Abstract: Abbreviations: BBB, blood-brain barrier; CNS, central nervous system; CSF, cerebrospinal fluid; CSPGs, chondroitin sulfate proteoglycans; EAE, experimental autoimmune encephalomyelitis; ECM, extracellular matrix; GAG, glycosaminoglycans; HMW hyaluronan, high-molecular weight hyaluronan; LMW hyaluronan, low-molecular weight hyaluronan; MBP, myelin basic protein; MMP, matrix metalloproteinase; MS, multiple sclerosis; MT-MMP, membrane-type matrix metalloproteinase; NAWM, normal appearing white matter; OPC, oligod… Show more

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Cited by 30 publications
(34 citation statements)
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References 274 publications
(676 reference statements)
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“…Upon toxin-induced demyelination, ASTRs transiently deposit several ECM proteins, including CSPGs and fibronectin, which add to resolve injury and promote recovery [221,[235][236][237][238][239]. The composition of the ECM affects OPC behavior; fibronectin increases OPC proliferation and migration and inhibits OPC differentiation [236,[239][240][241][242][243][244][245][246][247][248], while CSPGs inhibit OPC proliferation, migration and differentiation [239,[249][250][251][252][253]. Differentiation of neural stem cells into OPCs and finally into mature myelinating OLGs is, in addition to ECM composition, also dependent on the stiffness of the ECM [254].…”
Section: Astrocyte Diversity and Remyelinationmentioning
confidence: 99%
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“…Upon toxin-induced demyelination, ASTRs transiently deposit several ECM proteins, including CSPGs and fibronectin, which add to resolve injury and promote recovery [221,[235][236][237][238][239]. The composition of the ECM affects OPC behavior; fibronectin increases OPC proliferation and migration and inhibits OPC differentiation [236,[239][240][241][242][243][244][245][246][247][248], while CSPGs inhibit OPC proliferation, migration and differentiation [239,[249][250][251][252][253]. Differentiation of neural stem cells into OPCs and finally into mature myelinating OLGs is, in addition to ECM composition, also dependent on the stiffness of the ECM [254].…”
Section: Astrocyte Diversity and Remyelinationmentioning
confidence: 99%
“…Thus, in WM MS lesions, hMOLs populations were skewed to the transcriptionally different fully mature hMOL5 population and/or other populations were depleted. In favor of the latter is that in MS lesions adult OPCs lack the capability [120] and/or receive inhibitory signals [201,239] to form new hMOLs, which may represent the reduced abundance of the pre-myelinating hMOL6 [121]. In addition, increased transcript levels of myelin genes were observed in mature wmOLGs in MS [121], hinting to the involvement of mature OLGs in remyelination.…”
Section: Oligodendroglial Lineage Cell Diversity In White Matter Multmentioning
confidence: 99%
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“…In addition, wmOPCs are more susceptible to the detrimental effects of inflammatory mediators such as interferon‐γ (IFNγ, (Lentferink et al., 2018)). Astrocytes (ASTRs) play an important role in transient remodeling of the local signaling environment to facilitate remyelination upon CNS demyelination (Gudi, Gingele, Skripuletz, & Stangel, 2014; Jong, Wang, Oomkens, & Baron, 2020). Therefore, in addition to regional differences in OPCs, ASTRs from different brain regions may also contribute to regional differences in remyelination efficiency.…”
Section: Introductionmentioning
confidence: 99%
“…These ASTR subtypes are morphologically and functionally distinct, that is, protoplasmic ASTRs are morphological more complex and ensheath synapses, whereas fibrous ASTRs are specialized in providing structural support to myelinated axons and interact with the nodes of Ranvier (Oberheim et al., 2012). A dense astroglial scar is mainly formed in WM MS lesions and consists of persistent locally deposited extracellular matrix molecules, including proteoglycans and fibronectin that impair remyelination (reviewed in de Jong et al., 2020). While the role of ASTRs in remyelination in MS is still debated, a strong correlation exists between severe reactive glial scar formation and remyelination failure (Nair, Frederick, & Miller, 2008; Nash, Ioannidou, & Barnett, 2011).…”
Section: Introductionmentioning
confidence: 99%