BCAN - brevican | Elisa - Clia - Antibody - Protein

Background

Brevican (BCAN) is a member of the lectican family of proteoglycans, which are essential components of the extracellular matrix in the central nervous system (CNS). The lecticans, including aggrecan, versican, neurocan, and brevican, play crucial roles in the formation and maintenance of the neural extracellular matrix. Brevican is particularly abundant in the brain and spinal cord, where it contributes to the structural integrity and functionality of neural tissues. It was first identified in the early 1990s and has since been recognized for its involvement in various neural processes, including synaptic plasticity, axonal guidance, and neural repair.

Protein Structure

Brevican is a chondroitin sulfate proteoglycan, characterized by its core protein and attached glycosaminoglycan (GAG) chains. The protein structure of brevican includes several distinct domains:

1. N-terminal Domain: This domain contains a signal peptide sequence that directs the protein to the extracellular space.
2. IG-like Domain: An immunoglobulin (IG)-like domain follows the N-terminal domain and is involved in protein-protein interactions.
3. Lectin Domain: This domain allows brevican to bind carbohydrates, which is essential for its interaction with other extracellular matrix components.
4. EGF-like Domain: An epidermal growth factor (EGF)-like domain is present, which may be involved in cell adhesion and signaling.
5. C-terminal Domain: The C-terminal domain contains the binding sites for chondroitin sulfate chains, which are critical for the proteoglycan's function in the extracellular matrix.

The core protein of brevican is approximately 145 kDa, but with the addition of GAG chains, the molecular weight can increase significantly.

Classification and Subtypes

Brevican belongs to the family of lecticans, specifically classified under chondroitin sulfate proteoglycans due to its attached chondroitin sulfate chains. Unlike other members of the lectican family, brevican is primarily found in the CNS.

There are two main forms of brevican:

1. Full-length Brevican: This form includes the entire protein sequence along with its attached chondroitin sulfate chains.
2. Cleaved Brevican: Proteolytic cleavage of brevican can produce shorter forms, which can have different functional roles in the CNS. The cleaved forms are generated by various matrix metalloproteinases (MMPs) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes.

Function and Biological Significance

Brevican plays multiple roles in the CNS:

1. Extracellular Matrix Formation: Brevican contributes to the structural framework of the neural extracellular matrix, providing support and stability to neural tissues.
2. Synaptic Plasticity: It is involved in synaptic plasticity, influencing the strength and efficacy of synaptic connections. This is crucial for learning and memory processes.
3. Axonal Guidance: Brevican helps guide growing axons to their correct targets during neural development and regeneration.
4. Neural Repair: Following injury, brevican participates in the repair processes by modulating the extracellular environment and facilitating or inhibiting the regrowth of neural connections.
5. Cell Adhesion: Through its interaction with cell surface receptors and other extracellular matrix components, brevican influences cell adhesion and migration.

Clinical Issues

Abnormalities in brevican expression and function are associated with several neurological conditions:

1. Gliomas: Brevican is often overexpressed in gliomas, a type of brain tumor, where it promotes tumor cell invasion and proliferation. It serves as a biomarker for the diagnosis and progression of gliomas.
2. Neurodegenerative Diseases: Changes in brevican levels have been observed in neurodegenerative conditions like Alzheimer's disease, suggesting its involvement in the disease's progression.
3. Spinal Cord Injury: After spinal cord injury, brevican expression is upregulated, which can inhibit axonal regeneration and recovery of function. Modulating brevican levels could be a potential therapeutic strategy for improving outcomes after CNS injuries.

Summary

Brevican is a critical component of the extracellular matrix in the CNS, contributing to various neural processes such as synaptic plasticity, axonal guidance, and neural repair. Structurally, it comprises several domains that facilitate its interactions with other proteins and carbohydrates in the extracellular matrix. Brevican's role in maintaining neural integrity and function is underscored by its involvement in conditions like gliomas, neurodegenerative diseases, and spinal cord injuries. Understanding the precise mechanisms of brevican's actions and its regulation could provide valuable insights into therapeutic strategies for a range of neurological disorders.