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Chondroitin Sulfate Proteoglycans: Structure-Function Relationship with Implication in Neural Development and Brain Disorders

BioMed Research International, 2014 · DOI: 10.1155/2014/642798 · Published: May 14, 2014

Mental HealthNeurologyGenetics

Simple Explanation

Chondroitin sulfate proteoglycans (CSPGs) are molecules in the extracellular matrix that play roles in cell adhesion, growth, receptor binding, and cell migration. CSPGs are important in neuronal growth, especially in axon guidance after nervous system injuries. However, after an injury CSPGs can inhibit axon regeneration. Some CSPGs, such as aggrecan, versican, and neurocan, have been linked to brain disorders like bipolar disorder, schizophrenia, and ADHD.

Study Duration
Not specified
Participants
5061 patients and 9655 controls in one study, other studies had varying participant numbers or used cell lines.
Evidence Level
Review Article

Key Findings

  • 1
    Genetic variation in the NCAN gene (rs1064395) is a common risk factor for bipolar disorder and schizophrenia.
  • 2
    NCAN risk alleles are associated with altered cortical folding in schizophrenia patients.
  • 3
    Studies suggest a possible role for bipolar disorder risk alleles in children with ADHD.

Research Summary

This review discusses the structure and function of chondroitin sulfate proteoglycans (CSPGs) in both healthy states and in the context of genetic disorders affecting the brain. The reviewed studies highlight the role of CSPGs like NCAN, ACAN, and VCAN in physiological cellular processes and disorders such as those associated with inhibition of axonal regeneration, neurogenesis, and psychiatric conditions like bipolar disorder, schizophrenia, and ADHD. The review emphasizes the use of both experimental and in silico methods, including structural, crystallographic, and QSAR techniques, to identify structural changes underlying functional modifications induced by alterations in CSPG sequences.

Practical Implications

Drug Development

QSAR studies can aid in the design of new psychiatric drugs that target CSPGs, improving pharmacokinetic and pharmacodynamic properties.

Diagnostic Screening

Combining experimental and in silico techniques can lead to more reliable early identification of CSPG gene expression errors, potentially enabling new population screening tests for neurodevelopmental disorders.

Personalized Medicine

Understanding the molecular features of NCAN SNPs can help tailor treatments for psychiatric disorders based on individual genetic profiles.

Study Limitations

  • 1
    The precise mechanisms by which NCAN (rs1064395) SNP contributes to psychiatric disorders are not yet fully understood.
  • 2
    Many studies regarding antipsychotics and their effect on CSPGs show a narrow concentration window between efficacy and toxicity.
  • 3
    The exact mechanism by which NCAN, VCAN, or ACAN affects human tissues and the brain is not fully understood.

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