Roles of Eph receptors and ephrins in the normal and damaged adult CNS

Goldshmit, Yona; McLenachan, Samuel; Turnley, Ann M.

doi:10.1016/j.brainresrev.2006.04.006

Cited by 150 publications

(123 citation statements)

References 195 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…After damage to the adult spinal cord, members of the Eph family, along with their ligands (ephrins), accumulate in the proximal axon stump and reactive astrocytes and are thus implicated in glial scar formation [54] . The studies of the effects of ephrin-B2 on reactive astrocytes and EphB2 on meningeal fibroblasts demonstrate that cellular interplay mediated by ephrin-B2…”

Section: Eph/ephrinsmentioning

confidence: 99%

The glial scar in spinal cord injury and repair

2013

View full text Add to dashboard Cite

Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCi) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCi. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCi.Keywords: glial scar; spinal cord injury; axonal regeneration; astrocyte activation; reactive astrogliosis; neuroinflammation IntroductionSpinal cord injury (SCi) is a common and devastating central nervous system (CNS) insult that results in disruption of cord microstructure and is followed by limited neuronal regeneration and insufficient functional recovery in adult mammals. After severe SCi, and in response to changes in the local microenvironment, astrocytes, the most abundant glial cells in the CNS, transform into reactive astrocytes and undergo dramatic morphological changes [1] as well as massive variations in gene expression [2] . Reactive astrocytes, the major component of glial scars, along with other cells in the spinal cord and blood-borne cells leaking from the damaged blood-spinal cord barrier, participate in the process of scar formation [3] .From the historical perspective, a glial scar is recognized as an impediment to the regeneration of axons in the cord because of the irregular rearrangement of hypertrophic astrocytic processes, as well as major components of the axonal inhibitory extracellular matrix (ECM), including chondroitin sulfate proteoglycans (CSPGs) that are secreted by the reactive astrocytes [4] . Currently, increasing evidence is advancing our knowledge of the mechanism of the formation of glial scars after a lesion and the roles of glial scars in the regulation of neuro-inflammation and repair processes [5,6] .This article reviews the following: (1) the molecular and cellular properties of glial scar formation following SCi;(2) the roles of glial scar formation in axonal regeneration and neuro-inflammation; and (3) the current status of scarmodulating therapeutic strategies for spinal cord repair after injury. Molecular and Cellular Properties of Glial Scars Characterization of Glial ScarsTraumatic damage of the spinal cord can result in seallike scar tissue in the lesion zone, which is filled with dense cellular components and a connective matrix. Generally, the scar tissue is classified into two parts, fibrotic and glial. 422The fibrotic scar, primarily composed of invading fibrobl...

show abstract

Section: Eph/ephrinsmentioning

confidence: 99%

The glial scar in spinal cord injury and repair

2013

View full text Add to dashboard Cite

show abstract

“…For instance, disruption of the contact between astrocyte endfeets and vascular basement membranes by astroglia specific deletion of integrin β1, triggers a partial reactive state, including hypertrophy, GFAP, vimentin and Tenascin-C upregulation but excluding proliferation [69]. Other contact-related regulators of astrogliosis are Ephrins (Ephs) and their receptors [70]. These molecules are physiologically expressed in the CNS but become upregulated following injury in astrocytes possibly by inflammatory cytokines [70,71].…”

Section: Other Signalsmentioning

confidence: 99%

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Buffo

Rolando

Ceruti

2010

Biochemical Pharmacology

287

260

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Running title: Beneficial and detrimental outcomes of astrogliosis after central nervous system injury. Abbreviations:Ado, adenosine; AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate; AP1, activator protein1; AQP, acquaporin; BBB, blood-brain barrier; BDNF, brain-derived growth factor; bFGF, basic fibroblast growth factor; bHLH, basic helix loop helix; BMP, bone morphogenetic protein; CNS, central nervous system; CNTF, ciliary neurotrophic factor;COX-2, cyclooxigenase-2; CREB, cAMP response element binding; CSPGs, chondroitinsulphate proteoglycans; ERK, extracellular signal-regulated kinase; EGF, epidermal growth factor; Eph4A, ephrin 4A; Epo, erythropoietin; ET1, Endothelin 1; ET-R, endothelin receptor; GABA, gamma-aminobutyric acid; GDNF, glial cell-line derived neurotropic factor; GF, growth factor; GFAP, glial fibrillary acidic protein; GLAST, glutamate aspartate transporter; GLT1, glutamate transporter 1; GS, glutamine synthase; IFN , interferon-beta; IFNγ, interferon gamma; IGF1, insulin growth factor1; IL1β, interleukin 1 beta; IL2, interleukin 2; IL6, interleukin 6; IL10, interleukin 10; JAK, Janus protein tyrosine kinases; Lcn2, Lipocalin 2; MAPK, mitogen-activated protein kinase; MMP, matrix metalloprotease; mTOR, mammalian target of rapamycin; NFAT, nuclear factor of activated T cell; NFkB, nuclear factor kappa B; NGF, nerve growth factor; NT3, neurotrophin 3; p38MAPK, p38 mitogen-activated protein kinase; PTEN, phosphatase and tensin homolog; SOCS, suppressor of cytokine signaling; SOD, superoxide dismutase; STAT, signal transducers and activators of transcription; TGFα, transforming growth factor alpha;TGFβ, transforming growth factor beta; TNFα, tumor necrosis factor alpha; VCAM1, vascular cell adhesion molecule-1; VEGF, vascular endothelial growth factor. Page 4 of 63A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 4...

show abstract

“…Mammalian ephrinA1-ephrinA5 are attached to the membrane via a glycosylphosphatidylinositol (GPI) anchor, whereas ephrinB1-ephrinB3 are transmembrane proteins (Flanagan and Vanderhaeghen 1998;Goldshmit et al 2006;Kullander and Klein 2002). Ephrin ligands bind transmembrane receptor tyrosine kinase receptors (Eph).…”

Section: Guidance Cues During Development Ephrinsmentioning

confidence: 99%

“…Ephrin ligands bind transmembrane receptor tyrosine kinase receptors (Eph). There have been 13 mammalian Eph receptors identified to date; EphA1-EphA-8 and EphB1-EphB4, and EphB-6 (Flanagan and Vanderhaeghen 1998;Goldshmit et al 2006;Kullander and Klein 2002). The receptors are classified based on sequence homology and the ephrin ligands they bind, although it has recently been shown that receptors EphA4 and EphB2 can bind either A or B class Ephrins (Himanen et al 2004).…”

Section: Guidance Cues During Development Ephrinsmentioning

confidence: 99%

Molecular/genetic manipulation of extrinsic axon guidance factors for CNS repair and regeneration

Curinga

Smith

2008

Experimental Neurology

View full text Add to dashboard Cite

During development, guidance molecules play a key role in the formation of complex circuits required for neural functions. With the cessation of development, this exuberant growth process slows and stabilizes, and inhibitory molecules expressed by glia prevent initial attempts for axonal regeneration. In this review, we discuss the expression patterns and relative contribution of several guidance molecules on the regenerative process. Injury to the immature CNS or species capable of regenerating exhibit a complete or partial recapitulation of their developmental guidance patterns; whereas, similar injuries to adult mammals results in altered expression that acts to further hinder regeneration. Manipulations of guidance molecules after injury have been used to control detrimental effects of axon sprouting and target regenerating axons within the spinal cord.

show abstract

Roles of Eph receptors and ephrins in the normal and damaged adult CNS

Cited by 150 publications

References 195 publications

The glial scar in spinal cord injury and repair

The glial scar in spinal cord injury and repair

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Molecular/genetic manipulation of extrinsic axon guidance factors for CNS repair and regeneration

Contact Info

Product

Resources

About