Table 2.

The roles of MIF in PD.

Authors	Study design	Results
Schwarz et al. 1998 [36]	PD rat model: female Sprague-Dawley rats weighing 200 ± 250 g were injected twice of 6-OHDA into the right ascending nigrostriatal pathway and the ventral tegmental area	MIF-treated animals showed good survival of tyrosine hydroxylase positive ventral midbrain cells by reducing the number of microglial cells in the grafts.
Nicoletti et al. 2011 [37]	PD patients: mean age (years) = 61.7, gender (m/f) = 16/14 Control: mean age (years) = 57.3, gender (m/f) = 13/14	MIF serum levels increased in PD patients.
Li et al. 2019 [38]	Acute PD animal model: intraperitoneally injecting MPTP (20 mg/kg) into 7-week-old mice (n = 6) at 2-h intervals consecutively for four times Chronic PD animal model: injecting MPTP (15 mg/kg) into 7-week-old mice (n = 6) twice per week for five consecutive weeks SH-SY5Y cells	MIF increased in MPTP-induced mice as well as MPP+ induced SH-SY5Y cells. MIF siRNA and ISO-1 showed neuroprotective effect in MPP+ induced SY5Y cells by regulating inflammation, apoptosis and autophagy.
Cheng J et al. 2020 [39]	PD patients: n = 92 Control (age/sex-matched): n = 87 Mice with microglial deletion of Atg5 were generated by crossing the Atg5 locus floxed mice with Itgam/CD11b-Cre mice	MIF serum levels increased in PD patients. Inhibition of autophagy led to NLRP3 inflammasome activation in microglia by stimulation of the expression of MIF.
Zheng LT 2021 [15]	Microglia cells DA neurons	MIF selective inhibitor inhibited neuroinflammation and protected DA neurons.
Park et al. 2022 [5]	PD mouse models: 2 to 3-month-old C57BL/6 male and female mice with stereotaxic injection of α-syn PFF, AAV-α-syn or MPTP intoxication PAAN/MIF KO male and female mice	PAAN/MIF genetic depletion and nuclease activity mutant both alleviated neuronal loss and motor dysfunctions in PD animal model. MIF nuclease inhibitor significantly blocked α-syn PFF, AAV-α-syn overexpression or MPTP injection-induced neurodegeneration in vivo. MIF tautomerase inhibitors failed to inhibit MIF nuclease activity and parthanatic cell death.
Zhang et al. 2022 [16]	BV-2 cells Neurons	MIF inhibitors showed unti-neuroinflammatory and neuroprotective effects.