CASP3 and Cognitive impairment: CASP3 is the most important protease in the apoptotic signaling pathway and is considered a key mediator of neuronal apoptosis.[45] Considerable studies have shown that Casp3 expression is increased in the hippocampus of VD rats and that reducing apoptotic proteins in the hippocampus of VD rats can inhibit neuronal apoptosis, thereby alleviating the symptoms of VD and improving cognitive impairment.[46,47] The Bax/Bcl-2 ratio is an important indicator of apoptosis,[48] and a higher Bax/Bcl-2 ratio indicates a stronger pro-apoptotic capacity.