LAUSR

Microglia, the innate immune cells of the CNS, are critical for the regulation of the neuronal network, from the early neuronal developmental stages to adulthood (McGeer and McGeer, 2010). They act as brain macrophages, wiping out cell debris and phagocytizing viruses and bacteria. They support the development, maintenance, homeostasis, and repair of the brain (Eikelenboom and Veerhuis, 1996; Sajja et al., 2016). The resting state of microglia is sensitive to environmental stimuli. For example, stress conditions can activate aberrant microglia functioning, leading to the adverse onset of neurodegenerative and psychiatric disorders. In recent years, morphological ultra-structures and molecular states of microglia related to health and disease conditions have been reported. Recognition of microglia heterogeneity is fundamental to identify microglia-selectively therapies and uncover the underlying mechanisms that activate the reparative and regenerative functions of microglia (Lee et al., 2018). Pro-inflammatory microglia (M1-activated state) secrete proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase (iNOS), which typically lead to dysfunction following chronic activation. In contrast, neuroprotective microglia (M2 state) phagocytose cell debris and misfolded proteins, promote tissue repair and reconstruction of the extracellular matrix and support neuron survival mediated by neurotrophic factors. In this Research Topic, novel and well-characterized compounds are being discussed as microglia-selective neuro-therapies that can alter the functional state of microglia and modulate neuroinflammation (Figure 1). Gan et al. used oxymatrine (OMT), a natural quinoxaline alkaloid extracted from the root of Sophora flavescens, and provided evidence for its ability to reduce neuroinflammation in the 1-methyl-4-phenyl-1, 2, 3, 6tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). They also used 1methyl-4-phenylpyridinium (MPP)-induced mice primary microglia, primary murine neuron-microglia co-cultures, and primary microglia infected with cathepsin D (CathD)overexpressed lentivirus. OMT dose-dependently inhibited MPTP-induced motor deficits and provided dopamine neuroprotection. OMT also inhibited microglia activation following OPEN ACCESS