Combined analysis of the glia secretome and the CSF proteome: neuroinflammation and novel biomarkers

Abstract

Glial cells in the CNS are likely to communicate with other glial cells and neurons through secreted proteins. Glia-derived proteins also participate in neuroinflammation, which is a major component of neurodegenerative disease. Cerebrospinal fluid (CSF) is the biological fluid that best reflects the physiological or pathological conditions of the CNS. Proteins secreted from glial cells are often detected in the CSF. One of the major cellular sources of the highly abundant CSF proteins is glia. Combined analysis of secreted proteins of glial cells and CSF proteins of patients with inflammatory CNS disorders can provide new knowledge to the field of glia biology and neuron-glia interaction. The comparative analysis of the glia secretome and the CSF proteome would also facilitate the targeted proteomics-based discovery of new biomarkers for brain disease. Omics and systems biology approaches to glia and neuroinflammation will be a focus of future investigation and will enable an integrative understanding of inflammatory CNS disorders, such as neurodegenerative disease.

Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

“…We and others have previously investigated the secretome of brain glial cells [3,4,6,7,51,65,66]. Proteins secreted from glial cells have been shown to regulate neuron–glia communication and to play important roles in interglial interactions [67]. In the present study, we identified PAI-1 as the major secreted protein of glia through LC-MS/MS analysis of mouse mixed glial cultures.…”

Mapping of the secretome of primary isolates of mammalian cells, stem cells and derived cell lines

“…Proteins secreted from glial cells play an important role in the intercellular communication among cells in the central nervous system and contribute to proteome of cerebrospinal fluid. Astrocytes secrete numerous inflammatory mediators that are associated with tissue injury, inflammation and the pathogenesis of neurodegenerative disease such as Alzheimer's disease and Parkinson's disease [52]. Astrocyte secretome under normal or proinflammatory conditions have been partially mapped in primary cultures of astrocytes of mouse and rat origin.…”

Advances in the proteomic investigation of the cell secretome

“…However, challenges were encountered during analysis including dynamic range (affecting detection of low abundance biomarkers), difficulty assessing the relative contribution of a specific tissue to the proteome of a specific body fluid and the possibility of contamination by blood. To circumvent some of these confounding backgrounds when studying body fluids to mine for tissue-specific biomarkers, one can compare the proteome of a given body fluid with the secretome of cells originating from the tissue in proximity to this body fluid, such as previously documented in a combined analysis of the secretome of glial cells and the cerebrospinal fluid proteome [67]. …”