Mitochondrion-Specific Antioxidants as Drug Treatments for Alzheimer Disease

作者：Palacios Hector H; Yendluri Bharat B; Parvathaneni Kalpana; Shadlinski Vagif B; Obrenovich Mark E; Leszek Jerzy; Gokhman Dmitry; Gasiorowski Kazimierz; Bragin Valentin; Aliev Gjumrakch^*

来源：CNS & Neurological Disorders-Drug Targets, 2011, 10(2): 149-162.

• Alzheimer disease
• antioxidants
• mitochondria
• oxidative stress
• reactive oxygen species

Age-related dementias such as Alzheimer disease (AD) have been linked to vascular disorders like hypertension, diabetes and atherosclerosis. These risk factors cause ischemia, inflammation, oxidative damage and consequently reperfusion, which is largely due to reactive oxygen species (ROS) that are believed to induce mitochondrial damage. At higher concentrations, ROS can cause cell injury and death which occurs during the aging process, where oxidative stress is incremented due to an accelerated generation of ROS and a gradual decline in cellular antioxidant defense mechanisms. Neuronal mitochondria are especially vulnerable to oxidative stress due to their role in energy supply and use, causing a cascade of debilitating factors such as the production of giant and/or vulnerable young mitochondrion who's DNA has been compromised. Therefore, mitochondria specific antioxidants such as acetyl-L-carnitine and R-alphalipoic acid seem to be potential treatments for AD. They target the factors that damage mitochondria and reverse its effect, thus eliminating the imbalance seen in energy production and amyloid beta oxidation and making these antioxidants very powerful alternate strategies for the treatment of AD.

• 出版日期2011-3