Overcoming neurite‐inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix

Rowena, C.; Lau, Lorraine; Keough, Michael B.; Midha, Rajiv; Apte, Suneel S.

doi:10.1002/glia.22489

Cited by 79 publications

(59 citation statements)

References 77 publications

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“…In studies, CSPGs degradation by ADAMT4 showed that ADAMTS4 overcomes inhibition of axonal regeneration and promotes neurite outgrowth through a proteolytic mechanism [43]. ADAMTS4 caused a decrease in phosphocan accumulation [44], and ADAMTS4 increased the neurite outgrowth on rat neuron culture [45].…”

Section: Biochemical Enzymatic Degradations In Extracellular Space Thmentioning

confidence: 99%

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

Gürses¹,

Ural²,

Güleç³

et al. 2016

Aging and disease

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The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals.Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer's disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.

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Section: Biochemical Enzymatic Degradations In Extracellular Space Thmentioning

confidence: 99%

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

Gürses¹,

Ural²,

Güleç³

et al. 2016

Aging and disease

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“…Degradation of CSPG core proteins by matrix metalloproteinases, including a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), overcomes CSPG inhibition on neurite growth in culture (Cua et al, 2013). Local administration of ADAMTS-4 enhanced axonal regeneration/sprouting and promoted motor function recovery after SCI (Tauchi et al, 2012).…”

Section: Functions Of Reactive Scar Tissue After Cns Injurymentioning

confidence: 99%

Molecular mechanisms of scar-sourced axon growth inhibitors

Ohtake

2015

Brain Research

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Astrogliosis is a defense response of the CNS to minimize primary damage and to repair injured tissues, but it ultimately generates harmful effects by upregulating inhibitory molecules to suppress neuronal elongation and forming potent barriers to axon regeneration. Chondroitin sulfate proteoglycans (CSPGs) are highly expressed by reactive scars and are potent contributors to the non-permissive environment in mature CNS. Surmounting strong inhibition by CSPG-rich scar is an important therapeutic goal for achieving functional recovery after CNS injuries. Currently, enzymatic digestion of CSPGs with locally applied chondroitinase ABC is the main in vivo approach to overcome scar inhibition, but several disadvantages may prevent using this bacterial enzyme as a therapeutic option for patients. A better understanding of molecular mechanisms underlying CSPG function may facilitate development of new effective therapies to overcome scar-mediated inhibition. Previous studies support that CSPGs act by non-specifically hindering the binding of matrix molecules to their cell surface receptors through steric interactions, but two members of the leukocyte common antigen related (LAR) phosphatase subfamily, protein tyrosine phosphatase σ and LAR, are functional receptors that bind CSPGs with high affinity and mediate CSPG inhibition. CSPGs may also act by binding two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3. Thus, CSPGs inhibit axon growth through multiple mechanisms, making them especially potent and difficult therapeutic targets. Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries.

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“…Cua and collaborators (2013) reported that ADAMTS-4 was more efficient at degrading CSPGs and inducing subsequent neurite growth in vitro than chondroitinase ABC or MMPs [58]. …”

Section: Introductionmentioning

confidence: 99%

ADAMTS proteoglycanases in the physiological and pathological central nervous system

Lemarchant

Pruvost

Montaner

et al. 2013

J Neuroinflammation

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ADAMTS-1, -4, -5 and -9 belong to ‘a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)’ family and more precisely to the proteoglycanases subgroup based on their common ability to degrade chondroitin sulfate proteoglycans. They have been extensively investigated for their involvement in inflammation-induced osteoarthritis, and a growing body of evidence indicates that they may be of key importance in the physiological and pathological central nervous system (CNS). In this review, we discuss the deregulated expression of ADAMTS proteoglycanases during acute CNS injuries, such as stroke and spinal cord injury. Then, we provide new insights on ADAMTS proteoglycanases mediating synaptic plasticity, neurorepair, angiogenesis and inflammation mechanisms. Altogether, this review allows us to propose that ADAMTS proteoglycanases may be original therapeutic targets for CNS injuries.

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Overcoming neurite‐inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix

Cited by 79 publications

References 77 publications

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

Molecular mechanisms of scar-sourced axon growth inhibitors

ADAMTS proteoglycanases in the physiological and pathological central nervous system

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