Amyloid-beta-induced oxidative stress and mitochondrial dysfunction

Amyloid-beta (Aβ)-induced oxidative stress and mitochondrial dysfunction represent a critical pathological axis in the progression of Alzheimer's disease (Swerdlow et al., 2014). Aβ oligomers can localize to mitochondria, where they interact with proteins like Amyloid-binding alcohol dehydrogenase (ABAD) and components of the electron transport chain, leading to increased production of reactive oxygen species (ROS) and decreased ATP synthesis (Lustbader et al., 2004). This oxidative environment further promotes Aβ aggregation and impairs mitochondrial dynamics, including fusion, fission, and mitophagy (Butterfield et al., 2002). Consequently, the resulting bioenergetic failure and oxidative damage to lipids, proteins, and DNA trigger synaptic loss and neuronal death. Therapeutic approaches targeting this axis include monoclonal antibodies to clear Aβ, small molecule antioxidants to mitigate oxidative damage, and mitochondrial stabilizers designed to preserve cellular energy production.

Other names

Aβ-mediated mitochondrial toxicityAmyloid-beta-induced redox imbalanceMitochondrial dysfunction in Alzheimer's disease

Therapeutic strategies involve reducing Aβ burden to prevent downstream toxicity, utilizing antioxidants to scavenge reactive oxygen species, and employing mitochondria-targeted agents to maintain membrane potential and ATP production.