Abstract
Microglia, a type of innate immune cell of the brain, regulates neurogenesis, immunological surveillance, redox imbalance, cognitive and behavioral changes under normal and pathological conditions like Alzheimer’s, Parkinson’s, Multiple sclerosis and traumatic brain injury. Microglia produces a wide variety of cytokines to maintain homeostasis. It also participates in synaptic pruning and regulation of neurons overproduction by phagocytosis of neural precursor cells. The phenotypes of microglia are regulated by the local microenvironment of neurons and astrocytes via interaction with both soluble and membrane-bound mediators. In case of neuron degeneration as observed in acute or chronic neurodegenerative diseases, microglia gets released from the inhibitory effect of neurons and astrocytes, showing activated phenotype either of its dual function. Microglia shows neuroprotective effect by secreting growths factors to heal neurons and clears cell debris through phagocytosis in case of a moderate stimulus. But the same microglia starts releasing pro-inflammatory cytokines like TNF-α, IFN-γ, reactive oxygen species (ROS), and nitric oxide (NO), increasing neuroinflammation and redox imbalance in the brain under chronic signals. Therefore, pharmacological targeting of microglia would be a promising strategy in the regulation of neuroinflammation, redox imbalance and oxidative stress in neurodegenerative diseases. Some studies present potentials of natural products like curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane to suppress activation of microglia. These natural products have also been proposed as effective therapeutics to regulate the progression of neurodegenerative diseases. The present review article intends to explain the molecular mechanisms and functions of microglia and molecular dynamics of microglia specific genes and proteins like Iba1 and Tmem119 in neurodegeneration. The possible interventions by curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane on microglia specific protein Iba1 suggest possibility of natural products mediated regulation of microglia phenotypes and its functions to control redox imbalance and neuroinflammation in management of Alzheimer’s, Parkinson’s and Multiple Sclerosis for microglia-mediated therapeutics.
Highlights
The brain is one of the immune-privileged organs whose mechanisms of the immune response are poorly understood
Pathological conditions in the brain have been observed associated with increased oxidative stress which leads to redox imbalance
Natural Killer (NK) cell-deficient animals displayed increased inflammation in the CNS, as shown through glial fibrillary acidic protein (GFAP) and Iba1 (Mihara et al, 2008). Another chronic inflammatory neurodegenerative disease of the central nervous system (CNS) is multiple sclerosis (MS) which is characterized by demyelination and neuroaxonal damage that leads to the formation of lesions throughout the central nervous system (CNS)
Summary
The brain is one of the immune-privileged organs whose mechanisms of the immune response are poorly understood. It produces cytokines to maintain brain homeostasis, during development, adulthood and aging (Bitzer-Quintero and Gonzalez-Burgos, 2012; London et al, 2013; Burda and Sofroniew, 2014) They serve to communicate between the central nervous system and the peripheral immune system (Perry and Teeling, 2013). The microglia of aged organisms show activated state, morphological changes, alterations in telomere length, increased expression of MHCII, and CD11b. They limit neurogenesis during aging and induce neuroinflammatory reactivity in astrocytes, reduce synapse and pre-synaptic function. The malfunctioning of microglia cause redox imbalance and increased oxidative stress leading to the recruitment of lymphocytes from blood to damaged sites (London et al, 2013)
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