Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer’s Disease

Figure 2

Improving mitochondrial health in AD. In AD, the action of tau and Aβ generates impairment of the mitochondrial function causing fragmentation, depolarization, oxidative stress, and defects in axonal transport. Several strategies have been used to reduce mitochondrial failure in AD. These elements include antioxidants (systemic and mitochondria-targeted), inhibitors of mitochondrial dynamics, microtubules stabilizing drugs, and increase of mitochondrial biogenesis. Also, in this review, we propose the use of a “double mitochondrial therapy,” which means the combinatory use of mitotargeted antioxidants and activators of mitochondrial biogenesis. The use of these therapies can potentially reduce the mitochondrial fragmentation improving the mitochondrial network, restore the membrane potential (increasing ATP production and reducing ROS levels), and increase axonal transport. ΔΨ: mitochondrial membrane potential; VDAC1: voltage-dependent anion channel; HDAC6: histone deacetylase 6; Nrf2: nuclear factor erythroid 2-related factor 2; PGC1-α: peroxisome proliferator-activated receptor gamma-coactivator 1 alpha.