Epigenetic Modulation of Microglia Function and Phenotypes in Neurodegenerative Diseases

Abstract

Microglia-mediated neuroinflammation is one of the most remarkable hallmarks of neurodegenerative diseases (NDDs), including AD, PD, and ALS. Accumulating evidence indicates that microglia play both neuroprotective and detrimental roles in the onset and progression of NDDs. Yet, the specific mechanisms of action surrounding microglia are not clear. Modulation of microglia function and phenotypes appears to be a potential strategy to reverse NDDs. Until recently, research into the epigenetic mechanisms of diseases has been gradually developed, making it possible to elucidate the molecular mechanisms underlying the epigenetic regulation of microglia in NDDs. This review highlights the function and phenotypes of microglia, elucidates the relationship between microglia, epigenetic modifications, and NDDs, as well as the possible mechanisms underlying the epigenetic modulation of microglia in NDDs with a focus on potential intervention strategies.

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

“…In response to injury in the brain, neuroinflammation occurs in various cells, including neurons, microglia and astrocytes ( 62 ). In the acute phase, the damaged neurons and resident immune cells secrete inflammatory mediators and activate microglia, which are the first line of defense in the nervous system ( 63 ) that produce more inflammatory factors ( 62 , 64 ). Additionally, astrocytes that are activated by ischemia mediate inflammatory response to aggravate ischemic injury.…”

Role of Vitamin E and the Orexin System in Neuroprotection

“…Therefore, a reduction in the quantity of orexins could lead to an increase in microglial dysfunction with a consequent increase in the probability of developing neurodegenerative diseases [66]. As mentioned, the orexin systems play a pivotal role in neuroprotection and neuroinflammation [67,68]. OXA and OXB regulate the homeostatic mechanisms of energy balance and metabolism [64] through the activation of two G proteins (OX1, OX2) coupled to receptors, OX1R and OX2R, respectively [68].…”

“…As mentioned, the orexin systems play a pivotal role in neuroprotection and neuroinflammation [67,68]. OXA and OXB regulate the homeostatic mechanisms of energy balance and metabolism [64] through the activation of two G proteins (OX1, OX2) coupled to receptors, OX1R and OX2R, respectively [68]. Recent studies in neuronal cell cultures have shown that orexin plays a role in neuroprotection [64,65] by reducing lipid peroxidation, apoptosis and neuronal inflammation [39,[69][70][71].…”

Neuroprotective Epigenetic Changes Induced by Maternal Treatment with an Inhibitor of Soluble Epoxide Hydrolase Prevents Early Alzheimer′s Disease Neurodegeneration

“…Interestingly, maternal TPPU maintained low levels of Trem2 in both 5XFAD and WT mice. Microglia plasticity is modulated by epigenetic modifications including DNA methylation and histone acetylation reported here [ 57 , 58 ]. Therefore, we may speculate that microglia were imprinted early by epigenetic changes induced by TPPU treatment to a neuroprotective phenotype, although further investigations would be required to confirm the involvement of either HDACs inhibition or specific DNA gene methylation changes.…”