Brain extracellular matrix (ECM) is a highly organized system that consists of collagens, noncollagenous proteins, glycoproteins, hyaluronan, and proteoglycans. Recognized physiological roles of ECM include developmental regulation, tissue homeostasis, cell migration, cell proliferation, cell differentiation, neuronal plasticity, and neurite outgrowth. Aberrant ECM structure is associated with brain neurodegenerative conditions. This review focuses on two neurodegenerative conditions, schizophrenia and Alzheimer's disease, and summarizes recent findings of altered ECM components, including proteoglycans, glycosaminoglycans, proteins, and glycoproteins, and proteins and genes related to other brain components. The scope includes immunohistochemical, genomics, transcriptomics, proteomics, and glycomics studies, and a critical assessment of current state of proteomic studies for neurodegenerative disorders. The intent is to summarize the ECM molecular alterations associated with neurodegenerative pathophysiology. Graphical Abstract Brain extracellular matrix showing HSPGs, CSPGs, HA, collagens, and other glycoproteins.
Keywords: Alzheimer’s disease; Brain extracellular matrix; Glycosaminoglycans; Perineuronal nets; Proteoglycans; Schizophrenia.