Microglia M2 polarization (M2 polarization)

Microglia M2 polarization refers to the alternative activation state of the central nervous system's resident immune cells, characterized by an anti-inflammatory and neuroprotective profile [3, 6]. This phenotypic state is typically induced by cytokines such as Interleukin-4 and Interleukin-13, leading to the expression of tissue-repairing enzymes like Arginase-1 and phagocytic receptors like CD206 [1, 12]. In various neurological conditions, including Alzheimer's disease, stroke, and traumatic brain injury, the balance between pro-inflammatory (M1) and anti-inflammatory (M2) microglia is often disrupted, favoring chronic inflammation and progressive neurodegeneration [4, 6, 13]. Shifting this balance toward M2 polarization is a major therapeutic strategy aimed at resolving neuroinflammation and promoting recovery [1, 10, 11]. However, 'Microglia M2 polarization' represents a complex cellular process rather than a single molecular target, involving an intricate network of receptors and signaling pathways [5, 11]. While drugs like PPAR-gamma agonists and certain antidepressants can promote this shift in preclinical models, the heterogeneity and plasticity of microglial responses in the human brain remain significant challenges for clinical drug development [1, 9].

Other names

Alternative activation of microgliaM2 microglial phenotypeAnti-inflammatory microglial polarizationM2-like microgliaNeuroprotective microglial state

Pharmacological agents induce the M2 phenotype by activating anti-inflammatory signaling pathways such as the Interleukin-4 receptor/STAT6 axis, PPAR-gamma, and Nrf2, while concurrently suppressing pro-inflammatory M1 pathways like TLR4/NF-kappaB [1, 3, 10, 11]. This shift results in the upregulation of anti-inflammatory cytokines (e.g., IL-10, TGF-beta) and neurotrophic factors (e.g., BDNF, IGF-1) that promote neuronal survival and tissue homeostasis [2, 6, 8, 10].