Targeting the neural extracellular matrix in neurological disorders
Abstract
The extracellular matrix (ECM) is known to regulate important processes in neuronal cell development, activity and growth. It is associated with the structural stabilization of neuronal processes and synaptic contacts during the maturation of the central nervous system. The remodeling of the ECM during both development and after central nervous system injury has been shown to affect neuronal guidance, synaptic plasticity and their regenerative responses. Particular interest has focused on the inhibitory role of chondroitin sulfate proteoglycans (CSPGs) and their formation into dense lattice-like structures, termed perineuronal nets (PNNs), which enwrap sub-populations of neurons and restrict plasticity. Recent studies in mammalian systems have implicated CSPGs and PNNs in regulating and restricting structural plasticity. The enzymatic degradation of CSPGs or destabilization of PNNs has been shown to enhance neuronal activity and plasticity after central nervous system injury. This review focuses on the role of the ECM, CSPGs and PNNs; and how developmental and pharmacological manipulation of these structures have enhanced neuronal plasticity and aided functional recovery in regeneration, stroke, and amblyopia. In addition to CSPGs, this review also points to the functions and potential therapeutic value of these and several other key ECM molecules in epileptogenesis and dementia.
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PNNs tightly interdigitate with synaptic contacts on the soma and proximal dendrites of neurons.
“the unique, lattice--like structures that wrap around specific neurons in the brain and spinal cord called perineuronal nets (PNNs) that tightly interdigitate with synaptic contacts on the soma and proximal dendrites of neurons (Celio et al., 1998;Deepa et al., 2006;Soleman et al., 2013).”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Soleman et al., 2013
Many studies have identified molecules that block axonal sprouting after CNS injury, such as myelin proteins or chondroitin sulfate proteoglycans.
“There have been many studies of the molecules that block axonal sprouting after CNS injury, such as myelin proteins or chondroitin sulfate proteoglycans (CSPGs)8–10”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [9]
Axonal sprouting in the adult occurs in a limited manner after stroke, optic nerve lesions, spinal cord injury and in models of neurodegenerative diseases.
“Axonal sprouting in the adult occurs in a limited manner after stroke, optic nerve lesions, spinal cord injury and in models of neurodegenerative diseases8,9.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [9]
Much scientific study has focused on the molecular components of the injury response that block axonal sprouting, such as the glial growth inhibitors NogoA and the chondroitin sulfate proteoglycans.
“Much scientific study has focused on the molecular components of the injury response that block axonal sprouting, such as the glial growth inhibitors NogoA and the chondroitin sulfate proteoglycans8–10.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [9]
Impaired PNN formation and structure accompanied with altered synaptic plasticity is associated with psychiatric and neurological diseases such as schizophrenia and epilepsy.
“An impaired PNN formation and structure accompanied with altered synaptic plasticity is associated with a couple of psychiatric and neurological diseases such as schizophrenia and epilepsy, as reviewed recently62.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [62]
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- Authors
- Soleman, S., Filippov, M. A., Dityatev, A., & Fawcett, J. W.
- Affiliations
- University of Cambridge (GB)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Dityatev, A.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 253
- Pages
- 194-213
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1990555004
- Cited by
- 244
- References
- 44
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 17 · 2023: 13 · 2022: 16 · 2021: 26 · 2020: 23 · 2019: 14 · 2018: 22 · 2017: 16 · 2016: 28 · 2015: 21 · 2014: 26 · 2013: 1
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Ministry of Education and Science of the Russian Federation
- European Cooperation in Science and Technology (BM1001)
- 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
- extracellular matrix, chondroitin sulfate proteoglycans, perineuronal nets, neuroplasticity, central nervous system injury, stroke, amblyopia, neuronal regeneration, epileptogenesis, dementia, extracellular matrix degradation, functional recovery
- MeSH terms
- Animals, Extracellular Matrix, Humans, Nervous System Diseases, Neurons, Chondroitin Sulfate Proteoglycans, Extracellular Matrix Proteins
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