Mass spectrometry methods for analysis of extracellular matrix components in neurological diseases

The brain extracellular matrix (ECM) is a highly glycosylated environment and plays important roles in many processes including cell communication, growth factor binding, and scaffolding. The formation of structures such as perineuronal nets (PNNs) is critical in neuroprotection and neural plasticity, and the formation of molecular networks is dependent in part on glycans. The ECM is also implicated in the neuropathophysiology of disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Schizophrenia (SZ). As such, it is of interest to understand both the proteomic and glycomic makeup of healthy and diseased brain ECM. Further, there is a growing need for site-specific glycoproteomic information. Over the past decade, sample preparation, mass spectrometry, and bioinformatic methods have been developed and refined to provide comprehensive information about the glycoproteome. Core ECM molecules including versican, hyaluronan and proteoglycan link proteins, and tenascin are dysregulated in AD, PD, and SZ. Glycomic changes such as differential sialylation, sulfation, and branching are also associated with neurodegeneration. A more thorough understanding of the ECM and its proteomic, glycomic, and glycoproteomic changes in brain diseases may provide pathways to new therapeutic options.

Automated summary

The brain extracellular matrix (ECM), which is highly glycosylated, plays important roles in cell communication and neural function. Neuroprotection and neural plasticity rely on the formation of structures such as perineuronal nets (PNNs), which are influenced by glycans. Disorders like Alzheimer's disease, Parkinson's disease, and Schizophrenia are associated with dysregulation of ECM molecules and changes in glycomic profiles. Understanding these changes in brain diseases may lead to new therapeutic approaches.