Microglial activation state and secretome

Microglial activation state and secretome refer to the functional status and the collection of secreted factors of microglia, the primary innate immune cells of the central nervous system (CNS). Microglia can transition between various activation states, ranging from a homeostatic, surveillance phenotype to diverse reactive states such as the pro-inflammatory (M1-like) or neuroprotective (M2-like/DAM) phenotypes (Frontiers in Immunology, 2021; Springer Medicine, 2025). The secretome encompasses the cytokines, chemokines, and trophic factors released by these cells, which can either promote neuroinflammation and neuronal damage or support tissue repair and clearance of protein aggregates (NIH/PubMed, 2019; NIH/PubMed, 2024). In neurodegenerative conditions like Alzheimer's and Parkinson's disease, chronic microglial activation leads to a persistent neurotoxic secretome that accelerates disease progression (NIH/PubMed, 2025). Therapeutic strategies focus on modulating these states—often by targeting receptors like TREM2 or CD33—to suppress harmful inflammation and enhance the brain's internal clearance mechanisms (NIH/PubMed, 2024; Frontiers in Immunology, 2024).

Other names

Microglial polarizationMicroglial phenotypeMicroglial secretomeNeuroinflammatory secretomeActivated microglia conditioned medium

Modulation of microglial phenotypic polarization from neurotoxic (pro-inflammatory) to neuroprotective (anti-inflammatory or DAM) states and regulation of the neuroinflammatory secretome to reduce neuronal damage and enhance clearance of pathological aggregates (Frontiers in Immunology, 2021; NIH/PubMed, 2024).