Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

Figure 1

Mitochondrial damage in Alzheimer’s disease. Amyloid-𝛽 (A𝛽) overproduction damages mitochondria causing dysfunction of mitochondrial complexes I and IV, which result in reactive oxygen species (ROS) overproduction and adenosine triphosphate (ATP) depletion. In neurons, ATP depletion may lead to neurotransmission dysfunction and altered axonal transport, thus provoking mitochondrial dynamics abnormalities. ATP depletion also causes dysfunction of the ATP-dependent ion channels, leading to altered ion balance in the cytosol. ROS increase in turn leads to mitochondrial permeability transition pore (MPTP) aperture, which increases mitochondrial damage by allowing calcium entrance into the mitochondrial matrix, worsening the electron transport chain and oxidative phosphorylation disruption. ROS overproduction also causes membrane damage due to lipid peroxidation and triggering cell death mechanisms (apoptosis).