Table 2.

The effects of orexin on different molecular pathways of apoptosis.

Target	Specific proteins targeted	Effects of orexin	References
Effect on caspases	Caspase-3, Caspase-7, Caspase-9	Promotes apoptosis by inducing Caspase-3, Caspase-7, and Caspase-9	Voisin et al. (2022)
	Cytochrome C	Suppresses cleaved caspase-9 and caspase-3	Suo et al. (2018)
		Cytochrome c release	Xu et al. (2021b)
		Inhibits cytochrome C expression	Xu et al. (2021b)
		Stimulation of the enzyme phosphotyrosine phosphatase SHP-2, followed by the initiation of mitochondrial apoptosis mediated by cytochrome c	Marcos and Coveñas (2023)
Mitochondrial mechanism of apoptosis	Bcl-2, Bax	Increases Bcl-2 expression Decreases Bax expression Raise Bcl-2/Bax ratio	Safdar et al. (2021)
Effect of orexins on receptor-related mechanism of apoptosis	TNF-α	Reduce TNF-α-mediated inflammation Anti-apoptotic effect	Messal et al. (2018)
	Fas receptors	Reduces inflammation Potentially exhibits antiapoptotic effects	Dondelinger et al. (2016)
		Provides insights into chemotherapeutic intervention challenges with Fas ligand-mediated apoptosis	Wolpin and Mayer (2008), Segal and Saltz (2009), Voisin et al. (2011)
Endoplasmic reticulum stress and apoptosis	GRp87 IRE1α XBP1 PERK Unfolded Proteins, mTOR-XBP1	Prevents ER stress and inflammation	Tsuneki et al. (2022)
	Ca2+	At higher concentrations, orexins increase Ca2+ release from the endoplasmic reticulum and increase apoptosis	Xia et al. (2009)
Modulation of p53 activity	p53	Modulates p53 activity, leading to inhibition of apoptosis	Sokołowska et al. (2014)
Regulation of Caspase-2	Caspase-2	Reduces caspase-2 activity	Sokołowska et al. (2014)