Advanced search
Publication Cover
Expert Review of Neurotherapeutics Volume 10, 2010 - Issue 7
Submit an article Journal homepage
233
Views
73
CrossRef citations to date
0
Altmetric
Review

Antioxidant approaches for the treatment of Alzheimer’s disease

Hyun Pil Lee Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA; Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA
,
Xiongwei Zhu Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA; Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA
,
Gemma Casadesus Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA; Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA
,
Rudy J Castellani University of Maryland, MD, USA; University of Maryland, MD, USA
,
Akihiko Nunomura Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan; Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
,
Mark A Smith Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA; Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA
,
Hyoung-gon Lee Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA; Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA
&
George Perry Case Western Reserve University, OH, USA; College of Sciences, The University of Texas at San Antonio, San Antonio, TX 78249, USA; University of Texas at San Antonio, TX, USA. [email protected]; University of Texas at San Antonio, TX, USA. [email protected]
 show all
Pages 1201-1208 | Published online: 09 Jan 2014

References

  • Cummings JL, Cole G. Alzheimer disease. JAMA287, 2335–2338 (2002).
  • Alzheimer A. [An unusual disease of the cerebral cortex]. Zentralblatt fur Nervenkrankheiten25, 1134 (1906).
  • Smith MA, Casadesus G, Joseph JA et al. Amyloid-β and tau serve antioxidant functions in the aging and Alzheimer brain. Free Radic. Biol. Med.33, 1194–1199 (2002).
  • Lee HG, Perry G, Moreira PI et al. Tau phosphorylation in Alzheimer’s disease: pathogen or protector? Trends Mol. Med.11, 164–169 (2005).
  • Lee HG, Zhu X, Nunomura A et al. Amyloid β: the alternate hypothesis. Curr. Alzheimer Res.3, 75–80 (2006).
  • Selkoe DJ. Alzheimer’s disease results from the cerebral accumulation and cytotoxicity of Amyloid β-protein. J. Alzheimers Dis.3, 75–80 (2001).
  • Ashford JW. APOE genotype effects on Alzheimer’s disease onset and epidemiology. J. Mol. Neurosci.23, 157–165 (2004).
  • Teter B. ApoE-dependent plasticity in Alzheimer’s disease. J. Mol. Neurosci.23, 167–179 (2004).
  • Selkoe DJ. Alzheimer‘s disease: genotypes, phenotypes, and treatments. Science275, 630–631 (1997).
  • Bentahir M, Nyabi O, Verhamme J et al. Presenilin clinical mutations can affect γ-secretase activity by different mechanisms. J. Neurochem.96, 732–742 (2006).
  • Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science256, 184–185 (1992).
  • Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science297, 353–356 (2002).
  • Perry G, Nunomura A, Hirai K et al. Is oxidative damage the fundamental pathogenic mechanism of Alzheimer’s and other neurodegenerative diseases? Free Radic. Biol. Med.33, 1475–1479 (2002).
  • Perry G, Castellani RJ, Hirai K et al. Reactive oxygen species mediate cellular damage in Alzheimer disease. J. Alzheimers Dis.1, 45–55 (1998).
  • Harman D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol.11, 298–300 (1956).
  • Harman D, Eddy DE, Noffsinger J. Free radical theory of aging: inhibition of amyloidosis in mice by antioxidants; possible mechanism. J. Am. Geriatr. Soc.24, 203–210 (1976).
  • Smith MA, Sayre LM, Monnier VM et al. Radical ageing in Alzheimer‘s disease. Trends Neurosci.18, 172–176 (1995).
  • Schulz JB, Lindenau J, Seyfried J et al. Glutathione, oxidative stress and neurodegeneration. Eur. J. Biochem.267(16), 4904–4911 (2000).
  • Smith MA, Harris PL, Sayre LM et al. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc. Natl Acad. Sci. USA94, 9866–9868 (1997).
  • Reddy PH, Beal MF. Are mitochondria critical in the pathogenesis of Alzheimer’s disease? Brain Res. Brain Res. Rev.49, 618–632 (2005).
  • Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature430, 631–639 (2004).
  • Manczak M, Anekonda TS, Henson E et al. Mitochondria are a direct site of A β accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum. Mol. Genet.15, 1437–1449 (2006).
  • Reddy PH, Beal MF. Amyloid β, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol. Med.14, 45–53 (2008).
  • Hirai K, Aliev G, Nunomura A et al. Mitochondrial abnormalities in Alzheimer’s disease. J. Neurosci.21, 3017–3023 (2001).
  • Castellani R, Hirai K, Aliev G et al. Role of mitochondrial dysfunction in Alzheimer’s disease. J. Neurosci. Res.70, 357–360 (2002).
  • Wang X, Su B, Fujioka H et al. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer‘s disease patients. Am. J. Pathol.173, 470–482 (2008).
  • Wang X, Su B, Siedlak SL et al. Amyloid-β overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc. Natl Acad. Sci. USA105, 19318–19323 (2008).
  • Du H, Guo L, Fang F et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer‘s disease. Nat. Med.14, 1097–1105 (2008).
  • Russell RL, Siedlak SL, Raina AK et al. Increased neuronal glucose-6-phosphate dehydrogenase and sulfhydryl levels indicate reductive compensation to oxidative stress in Alzheimer disease. Arch. Biochem. Biophys.370, 236–239 (1999).
  • Mastrogiacomo F, Bergeron C, Kish SJ. Brain a-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. J. Neurochem.61, 2007–2014 (1993).
  • Moreira PI, Siedlak SL, Wang X et al. Autophagocytosis of mitochondria is prominent in Alzheimer disease. J. Neuropathol. Exp. Neurol.66, 525–532 (2007).
  • Simonian NA, Hyman BT. Functional alterations in Alzheimer’s disease: selective loss of mitochondrial-encoded cytochrome oxidase mRNA in the hippocampal formation. J. Neuropathol. Exp. Neurol.53, 508–512 (1994).
  • Yates CM, Butterworth J, Tennant MC et al. Enzyme activities in relation to pH and lactate in postmortem brain in Alzheimer-type and other dementias. J. Neurochem.55, 1624–1630 (1990).
  • Sayre LM, Perry G, Harris PL et al.In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer’s disease: a central role for bound transition metals. J. Neurochem.74, 270–279 (2000).
  • Bondy SC, Guo-Ross SX, Truong AT. Promotion of transition metal-induced reactive oxygen species formation by β-amyloid. Brain Res.799, 91–96 (1998).
  • Huang X, Atwood CS, Hartshorn MA et al. The Aβ peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry38, 7609–7616 (1999).
  • Nunomura A, Perry G, Pappolla MA et al. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer’s disease. J. Neurosci.19, 1959–1964 (1999).
  • Ramassamy C, Krzywokowski P, Bastianetto S et al. Apolipoprotein E, oxidative stress and EGb 761 in Alzheimer’s disease brain. In: Ginkgo Biloba Extract (EGb 761) Study: Lesson From Cell Biology. Packer L, Christen Y (Eds). Elsevier, Paris, France, 69–83 (1998).
  • Zhu X, Lee HG, Perry G et al. Alzheimer disease, the two-hit hypothesis: an update. Biochim. Biophys. Acta1772, 494–502 (2007).
  • Zhu X, Raina AK, Perry G et al. Alzheimer’s disease: the two-hit hypothesis. Lancet Neurol.3, 219–226 (2004).
  • Zhu X, Castellani RJ, Takeda A et al. Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the ‘two hit’ hypothesis. Mech. Ageing Dev.123, 39–46 (2001).
  • Kasa P, Rakonczay Z, Gulya K. The cholinergic system in Alzheimer’s disease. Prog. Neurobiol.52, 511–535 (1997).
  • Sims NR, Bowen DM, Allen SJ et al. Presynaptic cholinergic dysfunction in patients with dementia. J. Neurochem.40, 503–509 (1983).
  • DeKosky ST, Harbaugh RE, Schmitt FA et al. Cortical biopsy in Alzheimer‘s disease: diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. Intraventricular Bethanecol Study Group. Ann. Neurol.32, 625–632 (1992).
  • Whitehouse PJ. Cholinergic therapy in dementia. Acta Neurol. Scand. Suppl.149, 42–45 (1993).
  • Giacobini E. Cholinesterase inhibitors stabilize Alzheimer’s disease. Ann. NY Acad. Sci.920, 321–327 (2000).
  • Giacobini E. Do cholinesterase inhibitors have disease-modifying effects in Alzheimer’s disease? CNS Drugs15, 85–91 (2001).
  • Giacobini E. Long-term stabilizing effect of cholinesterase inhibitors in the therapy of Alzheimer’ disease. J. Neural. Transm. Suppl.62, 181–187 (2002).
  • Parsons CG, Gruner R, Rozental J et al. Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology32, 1337–1350 (1993).
  • Misztal M, Frankiewicz T, Parsons CG et al. Learning deficits induced by chronic intraventricular infusion of quinolinic acid – protection by MK-801 and memantine. Eur. J. Pharmacol.296, 1–8 (1996).
  • Wenk GL, Danysz W, Roice DD. Theeffects of mitochondrial failure upon cholinergic toxicity in the nucleus basalis. Neuroreport7, 1453–1456 (1996).
  • Zajaczkowski W, Quack G, Danysz W. Infusion of (+) -MK-801 and memantine – contrasting effects on radial maze learning in rats with entorhinal cortex lesion. Eur. J. Pharmacol.296, 239–246 (1996).
  • Bruce AJ, Boling W, Kindy MS et al. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat. Med.2, 788–794 (1996).
  • Melov S, Ravenscroft J, Malik S et al. Extension of life-span with superoxide dismutase/catalase mimetics. Science289, 1567–1569 (2000).
  • Adams JD, Jr., Klaidman LK, Odunze IN et al. Alzheimer’s and Parkinson’s disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. Mol. Chem. Neuropathol.14, 213–226 (1991).
  • Jenner P. Oxidative damage in neurodegenerative disease. Lancet344, 796–798 (1994).
  • Lohr JB, Browning JA. Free radical involvement in neuropsychiatric illnesses. Psychopharmacol. Bull.31, 159–165 (1995).
  • Sung S, Yao Y, Uryu K et al. Early vitamin E supplementation in young but not aged mice reduces Aβ levels and amyloid deposition in a transgenic model of Alzheimer's disease. FASEB J.18, 323–325 (2004).
  • Sano M, Ernesto C, Thomas RG et al. A controlled trial of selegiline, α-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N. Engl. J. Med.336, 1216–1222 (1997).
  • Morris MC, Evans DA, Bienias JL et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA287, 3230–3237 (2002).
  • Engelhart MJ, Geerlings MI, Ruitenberg A et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA287, 3223–3229 (2002).
  • Gray SL, Anderson ML, Crane PK et al. Antioxidant vitamin supplement use and risk of dementia or Alzheimer’s disease in older adults. J. Am. Geriatr. Soc.56(2), 291–295 (2008).
  • Isaac MG, Quinn R, Tabet N. Vitamin for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst. Rev.16(3), CD002854 (2008).
  • Petersen RC, Thomas RG, Grundman M et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N. Engl. J. Med.352(23), 2379–2388 (2005).
  • DeKosky ST, Williamson JD, Fitzpatrick AL et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA300(19), 2253–2262 (2008).
  • Reddy PH. Mitochondrial oxidative damage in aging and Alzheimer’s disease: implications for mitochondrially targeted antioxidant therapeutics. J. Biomed. Biotechnol.2006(3), 31372 (2006).
  • Sheu SS, Nauduri D, Anders MW. Targeting antioxidants to mitochondria: a new therapeutic direction. Biochim. Biophys. Acta.1762, 256–265 (2006).
  • Murphy MP, Smith RA. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu. Rev. Pharmacol. Toxicol.47, 629–656 (2007).
  • Cochemé HM, Kelso GF, James AM et al. Mitochondrial targeting of quinines: therapeutic implications. MitochondrionS94–S102 (2007).
  • James AM, Cochemé HM, Smith RA et al. Interactions of mitochondria-targeted and untargeted ubiquinones with the mitochondrial respiratory chain and reactive oxygen species. Implications for the use of exogenous ubiquinones as therapies and experimental tools. J. Biol. Chem.280, 21295–21312 (2005).
  • Salvemini D, Wang ZQ, Zweier JL et al. A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science286, 304–306 (1999).
  • Filipovska A, Kelso GF, Brown SE et al. Synthesis and characterization of a triphenylphosphonium-conjugated peroxidase mimetic: insights into the interaction of ebselen with mitochondria. J. Biol. Chem.280, 23113–23126 (2005).
  • Murphy MP, Echtay KS, Blaikie FH et al. Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: studies using a mitochondria-targeted spin trap derived from α-phenyl-N-tert-butylnitrone. J. Biol. Chem.278(49), 48534–48545 (2003).
  • Zhao K, Zhao GM, Wu D et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J. Biol. Chem.279(33), 34682–34690 (2004).
  • Massaad CA, Washington TM, Pautler RG et al. Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer’s disease. Proc. Natl Acad. Sci. USA106, 13576–13581 (2009).
  • Hayashi T, Shishido N, Nakayama K et al. Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-β peptide. Free Radic. Biol. Med.43, 1552–1559 (2007).
  • Nakamura M, Shishido N, Nunomura A et al. Three histidine residues of amyloid-β peptide control the redox activity of copper and iron. Biochemistry46, 12737–12743 (2007).
  • Cherny RA, Atwood CS, Xilinas ME et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron30, 665–676 (2001).
  • Crapper McLachlan DR, Dalton AJ, Kruck TP et al. Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet337, 1304–1308 (1991).
  • McLachlan DR, Smith WL, Kruck TPA. Desferrioxamine and Alzheimer’s disease: video home behavior assessment of clinical course and measures of brain aluminum. Ther. Drug Monit.15, 602–607 (1993).
  • Liu G, Men P, Harris PL et al. Nanoparticle iron chelators: a new therapeutic approach in Alzheimer disease and other neurologic disorders associated with trace metal imbalance. Neurosci. Lett.406, 189–193 (2006).
  • Liu G, Men P, Perry G, Smith MA. Nanoparticle and iron chelators as a potential novel Alzheimer therapy. Methods Mol. Biol.610, 123–144 (2010).
  • Doody RS, Gavrilova SI, Sano M et al. Effect of Dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomised, double-blind, placebo-controlled study. Lancet372, 207–215 (2008).
  • Grigorev VV, Dranyi OA, Bachurin SO. Comparative study of action mechanisms of dimebon and memantin on AMPA-and NMDA-subtypes glutamate receptors in rat cerebral neurons. Bull. Exp. Biol. Med.136(5), 474–477 (2003).
  • Lermontova NN, Redkozubov AE, Shevtsova EF et al. Dimebon and tacrine inhibit neurotoxic action of β-amyloid in culture and block L-type Ca(2+) channels. Bull. Exp. Biol. Med.132(5), 1079–1083 (2001).
  • Bachurin SO, Shevtsova EP, Kireeva EG et al. Mitochondria as a target for neurotoxins and neuroprotective agents. Ann. NY Acad. Sci.993, 334–344 (2003).
  • Nunomura A, Perry G, Aliev G et al. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol.60, 759–767 (2001).
  • Chan A, Paskavitz J, Remington R et al. Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s disease: a 1-year, open-label pilot study with an 16 month caregiver extension. Am. J. Alzheimers Dis. Other Demen.23(6), 571–585 (2009).
  • Risner ME, Saunders AM, Altman JF et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J.6, 246–254 (2006).
  • Iadecola C, Goldman SS, Harder DR et al. Recommendations of the National Heart, Lung, and Blood Institute working group on cerebrovascular biology and disease. Stroke37, 1578–1581 (2006).
  • Touyz RM, Schiffrin EL. Reactive oxygen species in vascular biology: implications in hypertension. Histochem. Cell Biol.,122, 339–352 (2004).
  • Vasdev S, Gill V, Singal P. Role of advanced glycation end products in hypertension and atherosclerosis: therapeutic implications. Cell Biochem. Biophys.49, 48–63 (2007).
  • Vaziri ND, Wang XQ, Oveisi F et al. Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension36, 142–146 (2000).
  • Vaziri ND, Rodriguez-Iturbe B. Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension. Nat. Clin. Pract. Nephrol.2, 582–593 (2006).
  • Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension44, 248–252 (2004).
  • Casserly I, Topol E. Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet363, 1139–1146 (2004).
  • Hasnain BI, Mooradian AD. Recent trials of antioxidant therapy: what should we be telling our patients? Cleve. Clin. J. Med.71, 327–334 (2004).
  • Tribble DL. AHA Science Advisory. Antioxidant consumption and risk of coronary heart disease: emphasison vitamin C, vitamin E, and β-carotene: a statement for healthcare professionals from the American Heart Association. Circulation99, 591–595 (1999).
  • Castellani RJ, Lee HG, Zhu X et al. Neuropathology of Alzheimer disease: pathognomonic but not pathogenic. Acta Neuropathol.111, 503–509 (2006).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.