Table 1. Notch signaling-related findings and their impact on disease outcomes in different animal models of MS.

Study	Animal Models	Notch-related Findings	Impact on Disease	References
Minter et al.	PLP/SJL EAE	GSI blocked Notch signaling nonspecifically	Improved clinical symptoms, decreased Th1 cytokines	[26]
Keerthivasan et al.	PLP/SJL EAE	Implication of Notch in Th17 Differentiation	GSI suppresses IL-17 production	[92]
Jurynczyk et al.	PLP/SJL EAE	Notch-3 targeted GSI reduced clinical illness	Reduced Th1 and Th17 cytokine levels and a notable decrease in clinical illness scores	[93]
Wongchana et al.	MOG/B6 EAE	Manipulating Notch-1 in macrophages did not impact the Th1 response	Disrupted macrophage-T-cell interaction	[94]
Fernلndez et al.	MOG/B6 EAE	Blocking Notch-1 alleviated EAE symptoms	Reduced demyelination, less microglia/astrocyte activation, T-cell infiltration, Th1/Th17 cells	[95]
Reynolds et al.	PLP/SJL EAE	DLL4 inhibition improved clinical disease	Reduced CD4+ T cells producing IFN-𝛾 and IL-17, reduced leukocyte infiltration.	[96]
Bassil et al.	MOG/B6 EAE	DLL4 inhibition shifted response to Th2/Treg	DLL4's role in Treg formation, decrease in the severity of clinical EAE	[97]
Elyaman et al.	MOG/B6 EAE	DLL1 manipulation impacted disease severity	Reduced CD4+IFN-𝛾+ cells	[98]
Zhu et al.	MOG/B6 EAE	Notch-1 on B cells promoted antibody production	Notch-1 signaling is crucial for antibodies	[99]
Palacios et al.	MOG/B6 EAE	JAG1 signaling correlated with increased CD25+Foxp3+ T cells	Improved EAE progression	[100]
Elyaman et al.	MOG/B6 EAE	Decreased EAE with JAG2 Signaling Prior to Antigen Vaccination	increase IL-9-mediated Treg-cell development	[101]
Elyaman et al.	MOG/B6 EAE	Aggravation of Disease with JAG2 Signaling During Simultaneous Immunization	aggravate the disease because IL-9 favors the proliferation of Th17 cells in an inflammatory environment	[101]
Fan et al.	Cuprizone model	Inhibition of Notch-1 facilitated remyelination	Improved recovery in mice during remyelination	[102]
Mathieu et al.	Cuprizone model	JAG1-expressing cells increased during injury	Implication of JAG1 in response to injury	[103]
Mathieu et al.	Cuprizone model	NG2 cells increased initially, then declined	Involvement of NG2 cells in myelin repair	[103]