title: Mitochondrial Pharmaceutics: A New Therapeutic Strategy to Ameliorate Oxidative Stress in Alzheimer's Disease.
abstract: Association between amyloid-β (Aβ) toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage has been demonstrated in the pathophysiology of Alzheimer's disease (AD). In the early stages of the disease, the defect in energy metabolism was found to be severe. This may probably due to the Aβ and ROS-induced declined activity of complexes in electron transport chain (ETC) as well as damages to mitochondrial DNA. Though clinically inconclusive, supplementation with antioxidants is reported to be beneficial especially in the early stages of the disease. A mild to moderate improvement in dementia is possible with therapy using antioxidants viz coenzyme Q10 (ubiquinone), α -lipoic acid, selenium, omega-3 fatty acids and vitamin E, emphasize their possible role as an adjuvant with the existing conventional treatment. Since mitochondrial dysfunction has been observed, a new therapeutic strategy called as 'Mitochondrial Medicine' which is aimed to maintain the energy production as well as to ameliorate the enhanced apoptosis of nerve cells, has been developed. Mitochondrial CoQ10, Szeto-Schiller peptide-31 and superoxide dismutase/ catalase mimetic, EUK-207 were the mitochondrial targeted agents demonstrated in experimental studies. This article discusses the mitochondrial impairment and the possible mitochondria targeted therapeutic intervention in AD.
authors.affiliation: Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur-680 555, Kerala, India. taajith@rediffmail.com.
authors.forename: Thekkuttuparambil A
authors.initials: TA
authors.lastname: Ajith
authors.forename: Gangadharan
authors.initials: G
authors.lastname: Padmajanair
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D004579:Electron Transport; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D013569:Synapses / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants