Table 1.

Role of cellular mechanisms in the regulation of microglia-mediated neuroinflammation

Mechanism	Mediator	Effects	Significance in AD	References
SphK1	N-AS	Acetylates COX and increases SPM SPM upregulates microglial phagocytic potential	Resolves neuroinflammation Reduces Aβ aggregates	[54]
COX/PGE2	PGE2 EP2 receptor of microglia	Deletion of PGE2 EP2 on microglia: Enhances phagocytosis of Aβ	Reduces neuroinflammation Reduces Aβ aggregates Maintain trophic factor and signalling	[55, 56]
NADPH oxidase-mediated metabolic pathway	Enzyme NADPH oxidase	Deletion of NADPH oxidase: Reduces ROS production Allows microglial switch from M1 to M2 phenotype	Reduces oxidative stress Decreases neuroinflammation	[57, 58]
CSFIR-mediated signalling	CSFIR	Deletion of CSFIR of microglia: Decreases microglia in niche Repopulation of new born microglia	Improves cognition Reduces Aβ burden Rescue dendrites Resolve neuroinflammation	[66, 67]
Calhms	Calhm1 Calhm2	Calcium homeostasis Aβ production Neuronal cell Viability Calcium homeostasis Neuro-inflammation	CALHM1 P86L polymorphism is associated with the incidence of AD Ablation of Cahm2 inhibits the production of inflammatory cytokines	[68] [69]
P2XY-NLRP3 pathway	PRXY	Regulates production of inflammatory cytokines via interaction with NLRP3	Inhibition of P2XY reduces neuroinflammation	[69,70,71, 72,73,74]