Table 2.

Role of PARP1 inhibitors in EAE mouse models

PARP1 inhibitors	Animal models	EAE modulation	Pathology alterations	Ref.
PJ34 (20 mg kg−1, i.p.) or PHE (20 mg kg−1, i.p.) Twice a day from day 0 to day 12	MOG35‐55‐EAE in C57BL/6J mice (female)	Resistance to EAE assessed up to day 12	Reduced dendritic cell (DC) infiltration in the spinal cord in PJ34 (or PHE)‐treated mice	[ 99 ]
PJ34 (20 mg kg−1, i.p.) or PHE (20 mg kg−1, i.p.) Twice daily from day 1 to day 16 (disease initiation) or from day 22 to day 34 (disease relapse)	PLP139‐151‐EAE in SJL mice (female)	Reduced clinical score of the disease initiation and of the disease relapse	Reduced inflammatory infiltrations and demyelination during the disease initiation; Reduced T cell number and Th17 cell number in spinal cord during the disease relapse	[ 99 ]
PJ34 (10 mg kg−1 oral) Twice daily from day 7 through the terminal sacrifice at day 22	MBP‐EAE in SJL mice (female)	Reduced EAE incidence, mortality, and severity	Reduced mRNA levels of CD4, CD8, CD11b, and CD68, interferon gamma (IFN‐γ), inducible nitric oxide synthase (iNOS), TNFa, intercellular adhesion molecule 1 (ICAM‐1) genes in the spinal cord; Reduced blood brain barrier (BBB) permeability	[ 100 ]
5‐AIQ (3 mg kg−1 i.p.) Daily from day 20 through the terminal sacrifice at day 60.	MOG35‐55‐EAE in nonobese diabetic (NOD) mice ‐ secondary progressive EAE #	Reduced severity during the progressive phase of EAE	Reduced demyelination and axonal loss, Reduced density of IBA1+ cells (microglia and macrophages) and GFAP+ astrocytes.	[ 14 ]
Olaparib	A mouse model of localized neuroinflammation elicited by intracerebral injection of TNFα	Not applicable	Diminished BBB permeability; Reduced leukocyte migration across the BBB; decreased neuroinflammation. These findings indicate that PARP1 inhibition may maintain BBB integrity in MS and/or EAE.	[ 101 ]
Veliparib Rucaparib, Talazoparib	A mouse model of Parkinson's disease elicited by intrastriatal injection of α‐synuclein preformed fibrils	Not applicable	Decreased dopamine neuronal loss. The finding indicates that PARP1 inhibition may protect neurons from damage during the time course of MS and/or EAE.	[ 12b ]
Olaparib (0.1 nM–10 µM)	In vitro oligodendrocyte culture	Not applicable	Olaparib induces OPC death and inhibits OPC differentiation into oligodendrocytes in the dish. These findings indicate that PARP1 inhibitors may exert a detrimental effect on oligodendrocyte survival and myelin repair in MS and/or EAE	[ 102 ]

^# a subsequent study demonstrated that MOG_35‐55‐EAE of nonobese diabetic (NOD) mice is not a progressive EAE model and that the seemingly progressive course seen in clinical score of MOG_35‐55‐EAE NOD mice is likely an artifact of data handling and interpretation^{[ 21 ]}