Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Miller, Gregory M.; Hsieh‐Wilson, Linda C.

doi:10.1016/j.expneurol.2015.08.015

Cited by 85 publications

(74 citation statements)

References 148 publications

(287 reference statements)

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“…CSPGs are diverse with respect to inhibiting or supporting axon growth at both protein and sugar-epitope levels 30,31 . Of the five growth-inhibitory CPSGs, WT scar-forming astrocytes increased only versican ramRNA, and significantly decreased neurocan and phosphacan (Fig.…”

Section: Resultsmentioning

confidence: 99%

Astrocyte scar formation aids central nervous system axon regeneration

Anderson

Burda

Ren

et al. 2016

Nature

1,459

1,423

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Summary Transected axons fail to regrow in the mature central nervous system (CNS). Astrocyte scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or deleting chronic astrocyte scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. In striking contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocyte scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth supporting molecules. Our findings show that contrary to prevailing dogma, astrocyte scar formation aids rather than prevents CNS axon regeneration.

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Section: Resultsmentioning

confidence: 99%

Astrocyte scar formation aids central nervous system axon regeneration

Anderson

Burda

Ren

et al. 2016

Nature

1,459

1,423

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“…). Recently, several lines of evidence have revealed the functional significance of the interaction between HS and canonical axon guidance molecules (Holt and Dickson ; Lee and Chien ; Lin ; Miller and Hsieh‐Wilson ; Van Vactor et al . ).…”

Section: Hs and Axon Guidancementioning

confidence: 99%

Proteoglycans and axon guidance: a new relationship between old partners

Masu

2016

Journal of Neurochemistry

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Neural circuits are formed with great precision during development. Accumulated evidence over the past three decades has demonstrated that growing axons are navigated toward their targets by the combined actions of attractants and repellents together with their receptors. It has long been known that proteoglycans, glycosylated proteins possessing covalently attached glycosaminoglycans, play a critical role in axon guidance; however, the molecular mechanisms by which proteoglycans regulate axon behaviors remain largely unknown. Glycosaminoglycans such as heparan sulfate and chondroitin sulfate are large linear polysaccharides composed of repeating disaccharide units that are highly modified by specific sulfation and epimerization. Recent biochemical and molecular biological studies have identified the enzymes that are involved in the biosynthesis of glycosaminoglycans. Interestingly, many mutants lacking glycosaminoglycan-synthesizing enzymes or proteoglycans in several model organisms show defects in specific nerve tract formation. In parallel, detailed biochemical studies have identified the molecular interactions between axon guidance molecules and glycosaminoglycans that have specific modification in their sugar chains. This review summarizes the structure and function of axon guidance molecules and glycosaminoglycans, and then tries to combine the knowledge from these studies to understand the role of proteoglycans from a new vantage point. Deciphering the sugar code is important for understanding the complicated nature of proteoglycans in axon guidance.

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“…They interface with metabolic state via lipid particles on liver cell proteoglycans [82]. They also guide morphological development [83], and even potentially behavior via their effects on neuronal migration [84]. …”

Section: – the Complex And Labile Forms Of Glycansmentioning

confidence: 99%

Glycomics: revealing the dynamic ecology and evolution of sugar molecules

Springer

Gagneux

2016

Journal of Proteomics

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Sugars are the most functionally and structurally diverse molecules in the biological world. Glycan structures range from tiny single monosaccharide units to giant chains thousands of units long. Some glycans are branched, their monosaccharides linked together in many different combinations and orientations. Some exist as solitary molecules; others are conjugated to proteins and lipids and alter their collective functional properties. In addition to structural and storage roles, glycan molecules participate in and actively regulate physiological and developmental processes. Glycans also mediate cellular interactions within and between individuals. Their roles in ecology and evolution are pivotal, but not well studied because glycan biochemistry requires different methods than standard molecular biology practice. The properties of glycans are in some ways convenient, and in others challenging. Glycans vary on organismal timescales, and in direct response to physiological and ecological conditions. Their mature structures are physical records of both genetic and environmental influences during maturation. We describe the scope of natural glycan variation and discuss how studying glycans will allow researchers to further integrate the fields of ecology and evolution.

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Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Cited by 85 publications

References 148 publications

Astrocyte scar formation aids central nervous system axon regeneration

Astrocyte scar formation aids central nervous system axon regeneration

Proteoglycans and axon guidance: a new relationship between old partners

Glycomics: revealing the dynamic ecology and evolution of sugar molecules

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