Pro-inflammatory Microglia (M1 phenotype) (M1 Microglia)

The M1 phenotype of microglia refers to the 'classically activated' pro-inflammatory state of the resident immune cells in the central nervous system (CNS) [StatPearls: Microglia]. This cellular state is typically triggered by exposure to interferon-gamma (IFN-γ) or lipopolysaccharides (LPS), resulting in the upregulation of surface markers such as CD86 and the release of neurotoxic mediators including nitric oxide (via iNOS) and reactive oxygen species [PMID: 26868314]. While this response is part of the innate defense against pathogens, chronic M1 activation is a major driver of neuroinflammation and neuronal death in neurodegenerative diseases like Alzheimer's and Parkinson's [PMID: 24321605, PMID: 30773664]. In a drug development context, the M1 phenotype is not a single molecular target but rather a pathological state; therapeutic strategies aim to either suppress M1-specific signaling pathways or promote a phenotypic shift toward the M2 'alternatively activated' neuroprotective state [PMID: 29033325]. Modern research increasingly views the M1/M2 paradigm as a simplified framework, as transcriptomic data reveals a highly plastic and diverse spectrum of microglial functional states in vivo [PMID: 28359086].

Other names

Classically activated microgliaM1-polarized microgliaNeurotoxic microgliaPro-inflammatory microglia state

Modulation of microglial polarization via inhibition of pro-inflammatory transcription factors (e.g., NF-κB, STAT1) or activation of anti-inflammatory pathways (e.g., PPAR-γ) to induce a phenotypic switch from the pro-inflammatory M1 state to the neuroprotective M2 state.