Brevican

Brevican is a brain-specific proteoglycan that plays a crucial role in the central nervous system (CNS) extracellular matrix (ECM). It is part of the lectican family, which also includes aggrecan, versican, and neurocan. Brevican is predominantly found in the neural tissue and is involved in various processes such as cell adhesion, neuronal migration, and the modulation of synaptic function.

Structure and Function

Brevican is a chondroitin sulfate proteoglycan with a core protein of approximately 145 kDa. It can exist in two forms: a full-length, membrane-bound form and a shorter, soluble form generated by the action of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteases. The core protein of brevican is composed of an N-terminal globular domain, a central region containing glycosaminoglycan (GAG) chains, and a C-terminal domain that interacts with other ECM components and cell surface receptors.

In the CNS, brevican contributes to the structural integrity of the ECM and influences neuronal plasticity, cell migration, and axon guidance. It is also implicated in the formation and maintenance of perineuronal nets (PNNs), specialized ECM structures that envelop certain neurons and are involved in regulating synaptic stability and plasticity.

Role in Disease

Alterations in brevican expression and function have been associated with several neurological disorders. For instance, increased levels of brevican are observed in the brain tissue surrounding glioma tumors, suggesting a role in tumor progression and invasion. Brevican is thought to modulate cell adhesion and migration, facilitating the spread of tumor cells through the brain ECM.

In addition, changes in brevican expression and the composition of PNNs have been linked to epilepsy. The remodeling of ECM, including alterations in brevican levels, may affect synaptic function and contribute to the hyperexcitability characteristic of epileptic tissue.

Research also suggests a potential role for brevican in neurodegenerative diseases such as Alzheimer's disease. Brevican levels are altered in the brains of Alzheimer's patients, and its interaction with other ECM components may influence the formation and stability of amyloid plaques.

Research and Therapeutic Potential

Understanding the precise roles of brevican in the CNS and its involvement in various diseases may offer new avenues for therapeutic intervention. For example, targeting the enzymes responsible for brevican processing or modulating its expression could potentially alter disease progression in gliomas, epilepsy, and neurodegenerative disorders.

See Also

• Extracellular matrix
• Proteoglycan
• Neuroplasticity
• Glioma
• Epilepsy
• Alzheimer's disease

References

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