Mitochondria- and Oxidative Stress-Targeting Substances in Cognitive Decline-Related Disorders: From Molecular Mechanisms to Clinical Evidence

Figure 2

The effects of Aβ, hyperphosphorylated tau, and standardized Ginkgo biloba extract (GBE) on mitochondrial function in AD. It has been shown that mitochondrial dysfunction is a key feature in AD and plays a pivotal role on the onset of the disease. While defining the chronologically first hallmark of the disease can be puzzling, there is evidence about mitochondrial dysfunction being the first hallmark at the early stages of AD with Aβ occurring as a result. Aβ has been shown to cause a decline in OXPHOS, taking place at the ETC, which leads to defective complexes IV and V and decreased ATP production. Faulty OXPHOS function results in the production of ROS which, when in excess, cannot be counterbalanced by the antioxidant enzymes like GSH-Px and SOD. ROS can cause membrane lipid peroxidation and instable MMP. Hyperphosphorylated tau inhibits complex I activity. However, GBE has been proven to reduce Aβ aggregation and tau hyperphosphorylation and to enhance OXPHOS, activities of complexes, and ATP levels, as well as to restore MMP. ROS and consequently lipid peroxidation are reduced due to GBE, while the extract has the ability to enhance SOD and GSH-Px activity and also induce mitochondrial biogenesis. ↓: represents increase; ⟂: represents inhibition.