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Cited by 131Proteoglycans and glycosaminoglycans researchNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity

Open access
Oohashi, Toshitaka, Edamatsu, Midori, Bekku, Yoko, Carulli, Daniela·2015·Experimental Neurology
DOI 10.1016/j.expneurol.2015.09.010
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Abstract

The hyaluronan and proteoglycanbinding link protein (Hapln) is a key molecule in the formation and control of hyaluronan-based condensed perineuronal matrix in the adult brain. This review summarizes the recent advances in understanding the role of Haplns in the formation and control of two distinct types of perineuronal matrices, one for "classical" PNN and the other for the specialized extracellular matrix (ECM) at the node of Ranvier in the central nervous system (CNS). We introduce the structural components of each ECM organization including the basic concept of supramolecular structure named "HLT model". We furthermore summarize the developmental and physiological role of perineuronal ECMs from the studies of Haplns and related molecules. Finally, we also discuss the potential mechanism modulating PNNs in the adult CNS. This layer of organized matrices may exert a direct effect via core protein or sugar moiety from the structure or by acting as a binding site for biologically active molecules, which are important for neuronal plasticity and saltatory conduction.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that hyaluronan and proteoglycan binding link proteins (Haplns) organize two hyaluronan-based extracellular matrices in the CNS: classical perineuronal nets (PNNs) and the specialized perinodal matrix at nodes of Ranvier. It synthesizes structural, developmental, and functional evidence that these matrices regulate neuronal plasticity, critical periods, and saltatory conduction.

Key findings

  • Haplns stabilize hyaluronan–lectican complexes within the “HLT” model, which the review extends from PNNs to the perinodal matrix; the intercellular space filled by ECM is reported as 20% of adult brain volume.
  • Hapln1/Crtl1 and Hapln4/Bral2 are neuronal PNN components. Hapln1/Crtl1 loss produces vestigial PNNs and enhanced visual and somatosensory plasticity, while Hapln4/Bral2 loss reduces brainstem/cerebellar PNNs and abolishes brevican localization.
  • Hapln2/Bral1 is a key perinodal component. Hapln2/Bral1-deficient mice show markedly decreased CNS conduction velocity despite unchanged nodal ion-channel clustering and node morphology, with reduced diffusion hindrance in white matter.
  • PNNs restrict experience-dependent plasticity and memory erasure; chondroitinase treatment restores juvenile-like plasticity and can improve recovery in injury or tau pathology models. The four Hapln proteins share 45–58% amino acid identity, and link modules are about 100 amino acids long.

Methods

  • Narrative review synthesizing published studies on Haplns, lecticans, hyaluronan, tenascin-R, PNNs, and the node of Ranvier.
  • No primary experimental design, sample, or new data are reported; the paper integrates structural, developmental, physiological, and knockout/knockdown findings from the cited literature.
  • Main analysis is conceptual: it describes the HLT model, compares PNN and perinodal ECM organization, and proposes specific Hapln–lectican pairing relationships.

Limitations

  • The paper states that the mechanisms by which PNNs restrict plasticity are not entirely elucidated, and it notes conflicting in vivo results on whether PNN digestion alters baseline neuronal activity.
  • Evident from the text: as a review, it provides no systematic search strategy, quantitative synthesis, or new experimental validation, and some claims are explicitly based on unpublished observations.
  • Evident from the text: several mechanistic proposals, such as specific Hapln–lectican micro-organization, are speculative and require further testing.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.expneurol.2015.09.010

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

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  • Premisecitation

    Hapln1/Crtl1 and versican G1 interact via their link modules.

    “In contrast, Hapln1/Crtl1 and versican G1 interaction occurred via their link modules (Matsumoto et al., 2003).”
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    • cites Matsumoto et al., 2003 source

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  • Interpretationreasoning

    The structure of neural extracellular matrix is similar to that of cartilage.

    “Those evidence indicate that the structure of neural ECM is similar to that of cartilage.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    The HLT model proposes that the supramolecular organization of perineuronal nets consists of hyaluronan, lecticans, and tenascin-R.

    “The current concept of supramolecular organization and assembly of PNN was first proposed by Ruoslahti (1996) and designated as “HLT (hyaluronan, lecticans and TN-R)” model by Yamaguchi (2000) (Fig. 2).”
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    • cites Ruoslahti, 1996 source

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  • Premisecitation

    Crtl1 was co-purified from P7 rat brain by immunoaffinity chromatography with the 1F6 monoclonal antibody against neurocan.

    “Crtl1 was also co-purified from P7 rat brain by immunoaffinity chromatography with the 1F6 mAb for neurocan (Meyer-Puttlitz et al., 1995).”
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    • cites Meyer-Puttlitz et al., 1995 source

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  • Premisecitation

    The G1 domain of lecticans binds backbone hyaluronan to form a tripartite complex with Hapln.

    “The G1 domain is important for its binding to backbone hyaluronan to form a tripartite complex with Hapln.”
    Quote in the paperSubstantial claim
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  • Classified as probably not a substantial claim. 6

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    Premisecitation

    Hapln1/Crtl1 and versican G1 do not bind directly in solution but form ternary complexes with a hyaluronan oligomer.

    “Hapln1/Crtl1and versican G1 did not bind directly to each other in solution yet formed ternary complexes with hyaluronan oligomer (Seyfrield et al., 2005).”
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    • cites Seyfrield et al., 2005

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    Premisecitation

    Perineuronal nets are reticular extracellular matrix structures that surround the cell bodies of many neurons and extend along their dendrites.

    “Perineuronal nets (PNNs) are reticular structures made of ECM molecules that surround the cell body of many neurons, and extend along their dendrites, which were first described by Camillo Golgi in 1882 (Celio et al., 1998).”
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    Premisenone given

    Haplns consist of an immunoglobulin module and two contiguous link modules.

    “Haplns consist of an immunoglobulin (Ig) module and two contiguous link modules (Fig. 1).”
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    Premisecitation

    The four Hapln proteins share between 45 and 58 percent amino acid identity, with extremely high homology in their link modules.

    “The four Hapln proteins share between 45 and 58% amino acid identity, and the homology in the link modules is extremely high (Bekku et al., 2003;Blundell et al., 2005).”
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    • cites Blundell et al., 2005 source

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    Premisereasoning

    The structure of Haplns is highly homologous to the G1 domain of lecticans, and both share the property of binding hyaluronan.

    “The structure of Haplns is highly homologous to that of the G1 domain of lecticans (Fig. 1), which share the common property of binding to hyaluronan.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Aggrecan is present on almost all PNN-positive neurons, while other lecticans are found on subpopulations of PNN neurons.

    “Aggrecan is present on almost all PNN-positive neurons, while other lecticans are found on subpopulations of PNN neurons, as shown by co-labeling of WFA with antibodies against different CSPG core proteins (Galtrey et al., 2008).”
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    Premisecitation

    Molecules crucial for perineuronal net assembly, namely hyaluronan synthases, link proteins, and aggrecan, are exclusively synthesized by neurons, whereas astrocytes, oligodendrocyte precursors, and oligodendrocytes produce other ECM molecules likely incorporated into the PNN.

    “As to the cellular origin of PNN components, molecules that are crucial for PNN assembly, namely HAS, link proteins and aggrecan, are exclusively synthesized by neurons, whereas astrocytes, oligodendrocyte precursors and oligodendrocytes produce other ECM molecules, which are then likely incorporated into the PNN (Carulli et al., 2006(Carulli et al., , 2007;;Lander et al., 1998; see table I).”
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    Premisecitation

    Perineuronal nets have been observed throughout the central nervous system of different organisms, including frogs, birds, and mammals.

    “PNNs have been observed throughout the CNS of different organisms, including frogs, birds and mammals (Celio et al., 1998;Balmer et al., 2009;Gaál et al., 2014;Morawski et al., 2009).”
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    Premisecitation

    Neurons in the cerebellar nuclei and visual cortex express HAS-2 and HAS-3, while neurons in the spinal cord express HAS-1 and HAS-3.

    “Neurons in the cerebellar nuclei and visual cortex express HAS-2 and -3, while neurons in the spinal cord express HAS-1 and -3 (Carulli et al., 2006(Carulli et al., , 2010;;Galtrey et al., 2008).”
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    Premisecitation

    WFA-positive nets are localized around different neuronal types, including parvalbumin-expressing GABAergic neurons in cortical areas, cortical pyramidal neurons, glutamatergic neurons in cerebellar nuclei, and glycinergic neurons of the medial nucleus of the trapezoid body.

    “WFA-positive nets are localised around different neuronal types, such as parvalbumin-expressing GABAergic neurons in cortical areas (see above), as well as cortical pyramidal neurons (Alpár et al., 2006;Hartig et al., 2001;Takahashi-Iwanaga et al., 1998;Wegner et al., 2003), glutamatergic neurons in the cerebellar nuclei (Carulli et al., 2006) and glycinergic neurons of the medial nucleus of the”
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    Premisecitation

    Perineuronal nets are most prominently displayed around GABAergic interneurons, with parvalbumin-expressing cells showing the highest level of colocalization.

    “The PNN is a unique ECM structure that is most prominently displayed around GABAergic interneurons, with parvalbumin expressing cells having the highest level of colocalization (Brückner et al., 1993;Celio and Chiquet-Ehrismann, 1993;Morris and Henderson, 2000).”
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    Interpretationcitation

    Hyaluronan synthases may act as anchor molecules for perineuronal nets because they retain the growing hyaluronan polymer while synthesizing and extruding it.

    “Furthermore, because HASs retain the growing hyaluronan polymer while synthesizing and extruding it from the cell surface (Toole, 2004), they might act as anchor molecules for the PNN.”
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    Interpretationcitation

    Hippocampal neurons lacking neurocan, brevican, tenascin-R, and tenascin-C display rudimentary perineuronal nets and reduced synapse number, suggesting that PNNs are important for synapse formation or stabilization.

    “In this model hippocampal neurons lacking neurocan, brevican, TN-R and TN-C display rudimentary PNNs and reduced synapse number, suggesting that PNNs are important for synapse formation/stabilization (Geissler et al., 2013).”
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    Premisecitation

    In mutant mice lacking Hapln4/Bral2, perineuronal nets in the brainstem and cerebellum are reduced, with complete lack of brevican and general attenuation of most other PNN components.

    “Similarly, in mutant mice lacking Hapln4/Bral2, which is mainly expressed in the brainstem and cerebellum, PNNs in these areas are reduced, with a complete lack of brevican and a general attenuation of the majority of the other PNN components (Bekku et al., 2012).”
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    • cites Bekku et al., 2012 source

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    Premisecitation

    Hyaluronan is synthesized by hyaluronan synthases located in the plasma membrane, and three isoforms synthesize hyaluronan chains of different lengths and at different speeds.

    “Hyaluronan is synthesized by hyaluronan sythases (HAS), which are located in the plasma membrane.Three isoforms of HAS exist (HAS-1, -2 and -3), encoded by individual genes, which synthesize hyaluronan chains of various length and at different speed, with HAS-1 and -2 generating hyaluronan chains of up to 2000 kD at fast speed, and HAS-3 producing hyaluronan shorter chains at slow speed (Itano et”
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    Premisecitation

    Contactin-1 interacts with CS-E in vitro, but this interaction mainly stimulates neurite outgrowth.

    “In vitro experiments show that contactin-1 interacts with CS-E, but the main effects of this interaction is the stimulation of neurite outgrowth (Mikami et al., 2009).”
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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    No evidence so far shows a relationship between CSPG receptors and PNNs.

    “However, no evidence so far exist showing a relationship between CSPG receptors and PNNs.”
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    Premisecitation

    CSPG digestion in organotypic hippocampal slices enhances motility of dendritic spines of CA1 pyramidal cells and induces spine head protrusions, in parallel with activation of β1-integrins and phosphorylation of focal adhesion kinase at synaptic sites.

    “CSPG digestion in organotypic hippocampal slices enhances the motility of dendritic spines of CA1 pyramidal cells and induces the appearance of spine head protrusions, in parallel with the activation of β1-integrins and phosphorylation of focal adhesion kinase at synaptic sites (Orlando et al., 2012).”
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    Interpretationcitation

    Perineuronal nets, rather than other modifications in the brain extracellular matrix, control central nervous system plasticity, and digestion of PNNs is how chondroitinase reactivates plasticity.

    “Notably, Carulli et al., (2010) showed that PNNs rather than other modifications in the brain ECM (such as changes in CSPG expression levels) control CNS plasticity, and digestion of PNNs is how chondroitinase reactivates plasticity.”
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    • cites Carulli et al., 2010 source

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    Premisecitation

    In adult mice lacking Hapln1/Crtl1, which exhibit vestigial perineuronal nets but no changes in overall levels of matrix components, plasticity in the visual and somatosensory systems is strongly enhanced.

    “Namely, in adult mice lacking Hapln1/Crtl1, which exhibit vestigial PNNs but no changes in the overall levels of matrix components, plasticity in the visual and somatosensory systems is strongly enhanced.”
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    • cites Carulli et al., 2010 source

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    Premisecitation

    Removal of chondroitin sulfate proteoglycans by chondroitinase in adult animals restores juvenile levels of plasticity in the rat visual cortex and allows complete recovery of visual acuity in rats that experienced monocular deprivation during the critical period.

    “They showed that removal of CSPGs by chondroitinase [a bacterial enzyme which degrades GAGs, including chondroitin sulfate and hyaluronan, disrupting the structure of the perineuronal net; see Galtrey and Fawcett (2007) for review] in adult animals restores juvenile levels of plasticity in the rat visual cortex, and allow a complete recovery of visual acuity in rats which experienced monocular”
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    • cites Pizzorusso et al., 2002 source

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    Premisecitation

    RPTPσ binds with high affinity to neurocan and aggrecan and strongly inhibits axon outgrowth and regeneration.

    “RPTPσ can bind with high affinity to neurocan and aggrecan and strongly inhibits axon outgrowth and regeneration (Sapieha et al., 2005;Shen et al., 2009;Fry et al., 2010;Lang et al., 2015).”
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    Premisecitation

    Reduced integrin activation occurs in neurons cultured on CSPG-coated substrate, which show growth inhibition; CSPG digestion releases the negative effects of CSPG on integrin activation and neurite outgrowth.

    “Reduced integrin activation is present in neurons cultured on substrate coated with CSPGs, which display growth inhibition and CSPG digestion release the negative effects of CSPG on integrin activation and neurite outgrowth (Afshari et al., 2010).”
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    Premisecitation

    The organization of specific ECM molecules into perineuronal nets in vivo requires appropriate stimuli and occurs during postnatal development, in concomitance with the end of the critical period for experience-dependent plasticity.

    “The organization of specific ECM molecules into PNNs in vivo requires the presence of appropriate stimuli and occurs during postnatal development, in concomitance with the end of the critical period for experience-dependent plasticity (Carulli et al., 2010;Kalb and Hockfield, 1990;McRae et al., 2007;Pizzorusso et al., 2002;Ye and Miao, 2013).”
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    Premisecitation

    Treatments with LAR-targeting peptides or LAR knockout significantly improve axonal growth and behavioral recovery after spinal cord injury.

    “LAR deletion in knock-out mice overcomes growth restriction of CSPGs on neurites in neuronal cultures, and treatments with LAR-targeting peptides or LAR knockout significantly improve axonal growth and behavioral recovery after spinal cord injury (Fisher et al., 2011;Xu et al., 2015).”
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    Premisecitation

    Sema3A binds PNNs via CS-E, which is enriched in PNNs.

    “Particularly, Sema3A has been shown to bind PNNs via CS-E (Dick et al., 2013), which is enriched in PNNs (Deepa et al., 2006).”
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    Interpretationcitation

    The HLT model made from PNN fits the perinodal matrix except that versican V2 is the most common lectican and aggrecan is absent at the node.

    “Of particular note is that the HLT model made from PNN fits to this PM except for the differences that vercican V2 is the most common lectican and aggrecan is absent at the node (Bekku et al., 2009;Dours-Zimmermann et al., 2009).”
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    Premisecitation

    Enriched environment promotes structural plasticity in the cerebellum, accompanied by strong PNN reduction and a putative increase in the excitatory/inhibitory ratio.

    “Enriched environment also promotes structural plasticity in the cerebellum, which is accompanied by a strong PNN reduction and a putative increase in the excitatory/inhibitory ratio.”
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    Premisecitation

    Peripheral nerve injury causes massive stripping of synapses on axotomized spinal motoneurons and induces disintegration of PNNs surrounding the motoneurons.

    “Peripheral nerve injury, which causes massive stripping of synapses on axotomized spinal motoneurons (Svensson et al., 1993), induces a disintegration of PNNs surrounding the motoneurons.”
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    Premisecitation

    When rats monocularly deprived during the critical period are reared in an enriched environment as adults, they show recovered visual acuity and cortical response to the deprived eye, and a decrease in PNN number in the visual cortex.

    “When rats which were monocularly deprived during the critical period are reared in an enriched environment as adults, they show recovered visual acuity and cortical response to the deprived eye and in parallel a decrease in PNN number in the visual cortex (Sale et al., 2007).”
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    Premisecitation

    CNS nerve conduction is markedly decreased in Hapln2/Bral1-deficient mice even though there are no differences between wild-type and mutant mice in clustering or transition of ion channels at the nodes or in tissue morphology around the nodes of Ranvier.

    “CNS nerve conduction is markedly decreased in Hapln2/Bral1-deficient mice even though there were no differences between wild-type and mutant mice in the clustering or transition of ion channels at the nodes or in the tissue morphology around the nodes of Ranvier.”
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    • cites Bekku et al., 2010

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    Premisecitation

    Exposure to enriched environment strongly promotes neuronal plasticity, enhancing learning and memory and leading to improved functional recovery after CNS lesion or disease.

    “Since the seminal work by Rosenzweig and coworkers (see Rosenzweig and Bennett (1996) for review), it is known that exposure to enriched sensory, motor, cognitive and social stimulation (i.e.enriched environment) strongly promotes neuronal plasticity, enhancing learning and memory and leading to improved functional recovery after different kinds of CNS lesion or disease (Bennet et al., 1969;Diamon”
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    Interpretationcitation

    The hyaluronan-associated ECM could serve as an extracellular ion pool at the perinodal extracellular space because both hyaluronan and chondroitin sulfate provide a strong negatively charged environment corresponding to the nodal diameter.

    “We thus proposed that the hyaluronan-associated ECM could serve as an”
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    Premisecitation

    Tnr-deficient mice are phenotypically normal but exhibit a significant decrease in conduction velocity compared with wild-type mice.

    “Tnr-deficient mice were phenotypically normal, although they exhibited a significant decrease in conduction velocity as compared with wild-type mice.”
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    • cites Weber et al., 1999 source

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    Premisecitation

    Unilateral labyrinthectomy induces partial degeneration of the vestibular nerve and loss of excitatory inputs to the vestibular nuclei, accompanied by a strong reduction of PNNs in those nuclei, which then re-form during compensatory axonal plasticity and behavioural recovery.

    “Accordingly, unilateral labyrinthectomy, which induces a partial degeneration of the vestibular nerve and thus a loss of excitatory inputs to the vestibular nuclei, is accompanied by a strong reduction of PNNs in those nuclei, which then re-form during compensatory axonal plasticity and behavioural recovery of the mice (Carulli, unpublished observations).”
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    Interpretationcitation

    The effect on conduction velocity differs among Vcan V0/V2-, Tnr-, and Hapln2/Bral1-deficient mice, probably due to differences in the degree of disturbed ECM assembly.

    “While the clustering of nodal sodium channels and paranodal structures appear unaffected in both Vcan V0/V2-and Tnr-deficient mice, effect on the conduction velocity is different in the three types of mutants (V0/V2-, Tnr-andHapln2/Bral1-deficient mice), probably due to the differences of degree of disturbed ECM assembly (Bekku et al., 2010;Dours-Zimmermann et al., 2009;Weber et al., 1999).”
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    Interpretationnone given

    Hapln2/Bral1 is an essential element of the perinodal matrix and plays a key role in the regulation of action potential conduction in myelinated axons.

    “Hapln2/Bral1 is an essential element of the PM and plays a key role in the regulation of action potential conduction in myelinated axons.”
    Quote in the paperSubstantial claim

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    Premisecitation

    CNS nodal ECMs do not play a primary role in recruiting Na+ channels at the nodes, but play a compensating role in assembling nodes or are important for stabilizing the nodes.

    “CNS nodal ECMs do not play a primary role to recruit Na + channels at the nodes, but play a compensating mechanism for assembling nodes or are important for stabilizing the nodes.”
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    Interpretationreasoning

    The phenotype of episodic falling syndrome may be explained by the biological function of brevican at the nodes, AIS, or PNNs, although a similar phenotype has not been reported in Bcan-deficient mice.

    “The phenotype may be explained by the biological function of the brevican at the nodes, AIS, or PNNs, although a similar phenotype has not been reported in the Bcan-deficient mice (Brakebusch et al., 2002).”
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    Interpretationown data

    The minimum unit of the perinodal matrix consists of Vcan V2, HA, and Hapln2/Bral1 in smaller axons, and a more complex matrix surrounds larger diameter axons.

    “Minimum unit of the matrix consists of Vcan V2, HA and Hapln2/Bral1 in smaller axon, and more complex matrix surrounds larger diameter axon.”
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  • May combine two claims.

    Premisecitation

    Congenital BCAN gene deletion is found in episodic falling syndrome, a neurological disorder with paroxysmal hypertonicity in dogs, which results from a CNS rather than a muscle defect.

    “Congenital BCAN gene deletion was found in episodic falling syndrome, a neurological disorder with paroxysmal hypertonicity in dogs, which results from a CNS rather than a muscle defect (Gill et al., 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gill et al., 2011

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Hapln1/Crtl1 and Hapln4/Bral2 are crucial components of PNNs, contributing to PNN formation/maintenance and to the control of plasticity exerted by PNNs.

    “Hapln1/Crtl1 and Hapln4/Bral2 are crucial components of PNNs, contributing to PNN formation/maintenance and to the control of plasticity exerted by PNNs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the CNS, oligodendrocytes do not contact the nodes, but astrocyte foot processes contact nodes to some extent.

    “In the CNS, oligodendrocytes themselves do not contact the nodes but astrocyte foot processes contact nodes to some extent (Bekku et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bekku et al., 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Brevican enrichment in the AIS is mediated via direct interaction with NF186, which is diminished by knockdown of NF186.

    “Brevican enrichment in the AIS was mediated via direct interaction with NF186, which was diminished by a knockdown of NF186 (John et al., 2006;Hedstrom et al., 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites John et al., 2006 source

      Not checked in the free run.

    • cites Hedstrom et al., 2007 source

      Not checked in the free run.

44 of 44

  • The paper relies on this without support.

    PNNs are composed of growth-inhibitory molecules such as CSPGs.

    “Because PNNs are composed of growth-inhibitory molecules, such as CSPGs, they may exert their inhibitory effect through these components, and the efficiency of chondroitinase treatment in promoting axonal sprouting points in this direction.”

  • The paper relies on this without support.

    Integrins have growth-promoting activity that depends on the substrate neurons contact.

    “Integrins possess a growth-promoting activity which depends on the substrate which the neurons contact.”

  • The paper relies on this without support.

    Clustering of voltage-gated Na+ channels is the most important functional requirement for action potential generation at the AIS and regeneration at nodes of Ranvier.

    “Clustering of voltage-gated Na + channels is most important functional requirement to generate action potentials at the AIS and regenerate action potentials at the nodes of Ranvier.”

  • The paper relies on this without support.

    The adult CNS retains a certain degree of plasticity.

    “In parallel with recent discoveries that highlight that the adult CNS retains a certain degree of plasticity, activity-dependent changes to PNNs have been shown to occur even in the adult CNS.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Binding of the N-terminal of CSPG to hyaluronan chains is stabilised by Hapln, and the C-terminals of three CSPG molecules link with trimeric tenascin-R.

    “While binding of the N-terminal of CSPG to hyaluronan chains is stabilised by Hapln, the C-terminals of three CSPG molecules will link with the trimeric tenascin-R [19–21].”

    From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [21]

  • Perineuronal nets (PNs) are polyanionic, chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain neurons.

    “As part of the extracellular matrix (ECM), perineuronal nets (PNs) are polyanionic, chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain neurons, known to be affected in various neural diseases.”

    From Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep (2017) · cites this paper as Oohashi et al., 2015

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Cited by

Sorted by citations

Authors
Oohashi, T., Edamatsu, M., Bekku, Y., & Carulli, D.
Affiliations
  • Okayama University (JP)
  • NYU Langone Health (US)
  • Neuroscience Institute Cavalieri Ottolenghi (IT)
Corresponding author
Oohashi, Toshitaka
ORCID
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2015-12
Volume
274
Issue
Pt B
Pages
134-144
ISSN
0014-4886 (ISSN-L)
DOI
10.1016/j.expneurol.2015.09.010
OpenAlex
W1808361382
Semantic Scholar
9921323d2ae02f840f3410a83ff7dce02e1a16a5
Cited by
131
References
53
Citations by year
2026: 9 · 2025: 14 · 2024: 15 · 2023: 11 · 2022: 11 · 2021: 19 · 2020: 15 · 2019: 11 · 2018: 13 · 2017: 10 · 2016: 3
FWCI
0.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
Funders
Ministry of Education, Culture, Sports, Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
brain extracellular matrix, nodes of Ranvier, neuroplasticity, saltatory conduction, supramolecular structure, central nervous system development
MeSH terms
Proteoglycan Link Protein, Animals, Brain, Extracellular Matrix, Humans, Neuronal Plasticity, Neurons, Proteoglycans, Extracellular Matrix Proteins

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