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Beyond presynaptic deficits, chronic dopamine depletion leads to postsynaptic adaptations, including downregulation of D2/3 receptors and inflammationmediated desensitization of downstream signaling pathways [201]

Gut dysbiosis is associated with instability in the composition of the gut microbiota, a reduction in the abundance of beneficial taxa, a concomitant increase in the abundance of opportunistic bacteria and pathogens, and overall changes in microbial diversity (20, 46)

Additionally, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of PD, UDCA treatment decreased levels of tumor necrosis factor (TNF-), interleukin-6 (IL-6), IL-1 and interferon- (IFN-) and prevented MPTP-induced degeneration of DA neurons, whose mechanism correlates with the inhibition of phosphorylation of JNK and p38MAPK to against neuroinflammation [130]

Subsequent flow cytometric analysis of NRF2 expression in ILC2s revealed that melatonin treatment significantly increased NRF2 protein levels ( Figure 6D )

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