Ceramides in Alzheimer’s Disease: Key Mediators of Neuronal Apoptosis Induced by Oxidative Stress and Aβ Accumulation

Figure 2

Role of ceramides in neuronal apoptosis. Overexpressed ceramides may provoke apoptosis by directly participating in ROS generation, through modulation of mitogen-activated protein kinases (MAPKs) signalling pathways, and by inhibition of prosurvival phosphatidylinositol 3-kinase (PI3-K)/Akt pathway via protein phosphatase 2A (PP2A) dephosphorylation, leading to activation of Bad and glycogen synthase 3β (GSK-3β). These cascades of biochemical alterations ultimately lead to neuronal death by diverse mechanisms, including depolarization and permeabilization of mitochondria (), Bcl-2 depletion and Bax increase, cytochrome c release, and caspase-3 activation.