Mitochondrial Oxidative Damage in Aging and Alzheimer's Disease: Implications for Mitochondrially Targeted Antioxidant Therapeutics

[摘要] The overall aim of this article is to review current therapeuticstrategies for treating AD, with a focus on mitochondriallytargeted antioxidant treatments. Recent advances in molecular,cellular, and animal model studies of AD have revealed thatamyloid precursor protein derivatives, including amyloid beta(Aβ)monomers and oligomers, are likely key factors in tauhyperphosphorylation, mitochondrial oxidative damage, inflammatorychanges, and synaptic failure in the brain tissue of AD patients.Several therapeutic strategies have been developed to treat AD,including anti-inflammatory, antioxidant, and antiamyloidapproaches. Among these, mitochondrial antioxidant therapy hasbeen found to be the most efficacious in reducing pathologicalchanges and in not producing adverse effects; thus, mitochondrialantioxidant therapy is promising as a treatment for AD patients.However, a major limitation in applying mitochondrial antioxidantsto AD treatment has been the inability of researchers to enhanceantioxidant levels in mitochondria. Recently, however, there hasbeen a breakthrough. Researchers have recently been able topromote the entry of certain antioxidants—including MitoQ,MitoVitE, MitoPBN, MitoPeroxidase, and amino acid andpeptide-based SS tetrapeptides—into mitochondria, severalhundred-fold more than do natural antioxidants. Once in themitochondria, they rapidly neutralize free radicals and decreasemitochondrial toxicity. Thus, mitochondrially targetedantioxidants are promising candidates for treating AD patients.

[学科分类] 基础医学