Tilting homeostatic and dyshomeostatic microglial balance in health and disease: transforming growth factor-beta1 as a critical protagonist

作者：Nicolas Hugues, Yu Luo · 发表于：Neural Regeneration Research · 年份：2024 · DOI：10.4103/nrr.nrr-d-24-00700 · 被引用次数：3 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Nuclear Receptors and Signaling、S100 Proteins and Annexins

Adult microglia, by continuously sensing changes in their environment and communicating with nearly all brain cell types, are considered to be the immune sentinels of the brain. In the healthy central nervous system (CNS), microglia display a unique molecular homeostatic signature (i.e., Tmem119, P2ry12, Sall1, Siglech, Gpr34, and Hexb) (Figure 1A). These homeostatic microglia are distinct from activated microglia, the signature of which is highly microenvironment- and cellular context-dependent (Butovsky and Weiner, 2018; Paolicelli et al., 2022; Figure 1). The type and severity of insult, as well as the duration of stimulation, could influence either the beneficial or detrimental nature of the microglial response. On one hand, microglia could exert a protective function through phagocytosis and clearance of pathological protein aggregates. On the other hand, an excessive uptake of protein aggregates by microglia could lead to impairment of microglial phagocytic ability, induction of neuroinflammation, and eventually neurodegeneration. Neurodegenerative diseases, chronic neuroinflammatory states, and advanced aging could each induce dyshomeostatic profiles that can share some similarities while possessing distinct gene expression profiles (e.g., microglial neurodegenerative phenotype, MGnD; disease-associated microglia, DAM; aging-related microglia) (Paolicelli et al., 2022). This switch to a dyshomeostatic profile is reflected by an increased expression of neurodegenerative...