Mitochondrial dysfunction-A pharmacological target in Alzheimer's disease

Molecular Neurobiology

Volumn 46, Issue 1, 2012, Pages 136-150

  Eckert, Gunter P ^a   Renner, Kathrin ^b   Eckert, Schamim H ^a   Eckmann, Janett ^a   Hagl, Stephanie ^a   Abdel Kader, Reham M ^a,d   Kurz, Christopher ^a   Leuner, Kristina ^a,c   Muller, Walter E ^a  

^a GOETHE UNIVERSITY   (Germany)

^b UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^c UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^d German University in Cairo   (Egypt)

Author keywords

Alzheimer's disease; Mitochondrial dysfunction; Neurodegenerative disease

Indexed keywords

ALPHA TOCOPHEROL; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; ANTIOXIDANT; ASCORBIC ACID; CURCUMIN; DIMEBON; DOCOSAHEXAENOIC ACID; GINKGO BILOBA EXTRACT; GLUTAMIC ACID; METHYLENE BLUE; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; NATURAL PRODUCT; OMEGA 3 FATTY ACID; PIRACETAM; PLACEBO; POLYUNSATURATED FATTY ACID; PROTEIN BCL 2; REACTIVE OXYGEN METABOLITE; ROTENONE; SIMVASTATIN; TAU PROTEIN;

AGING; ALZHEIMER DISEASE; APOPTOSIS; ARTICLE; BRAIN METABOLISM; BRAIN MITOCHONDRION; COGNITION; COGNITIVE DEFECT; DEGENERATIVE DISEASE; DEMENTIA; DIETARY INTAKE; DRUG APPROVAL; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG TARGETING; ENZYME ACTIVITY; FISH; FOOD AND DRUG ADMINISTRATION; GINKGO BILOBA; HUMAN; HUNTINGTON CHOREA; LOW DRUG DOSE; MEMORY; MEMORY DISORDER; META ANALYSIS (TOPIC); MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL PERMEABILITY; NERVE CELL; NEUROLOGIC DISEASE; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); STREPTOZOCIN DIABETES;

EID: 84868147363     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-012-8271-z     Document Type: Article

References (210)

1. Muller WE, Eckert A, Kurz C, Eckert GP, Leuner K (2010) Mitochondrial dysfunction: common final pathway in brain aging and Alzheimer's disease-therapeutic aspects. Mol Neurobiol 41 (2-3):159-171
2. Nijtmans LGJ, Ugallde C, van den Heuvel LP, Smeitink JAM (2004) Function and dysfunction of the oxidative phospharylation system. In: Koehler C, Bauer MF (eds) Mitochondrial function and biogenetics. Springer Inc., Heidelberg, pp 149-167
3. Mokranjac D, Neupert W (2009) Thirty years of protein translocation into mitochondria: unexpectedly complex and still puzzling. Biochim Biophys Acta 1793(1):33-41
4. Palmieri F, Pierri CL (2010) Structure and function of mitochondrial carriers-role of the transmembrane helix P and G residues in the gating and transport mechanism. FEBS Lett 584(9):1931-1939
5. Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakay JL, Parker N (2004) Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 37(6):755-767 (Pubitemid 39078548)
6. Smeitink J, van den Heuvel L, DiMauro S (2001) The genetics and pathology of oxidative phosphorylation. Nat Rev Genet 2 (5):342-352 (Pubitemid 33673072)
7. Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, Hill DE, Vidal M, Evans JG, Thorburn DR, Carr SA, Mootha VK (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134(1):112-123 (Pubitemid 351916708)
8. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38(5):515-517
9. Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38(5):518-520
10. Gimenez-Roqueplo AP, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rotig A, Jeunemaitre X (2001) The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am J Hum Genet 69(6):1186-1197 (Pubitemid 33124200)
11. Liesa M, Palacin M, Zorzano A (2009) Mitochondrial dynamics in mammalian health and disease. Physiol Rev 89(3):799-845
12. Detmer SA, Chan DC (2007) Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8(11):870-879 (Pubitemid 47622562)
13. Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280 (28):26185-26192 (Pubitemid 41022214)
14. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1-13
15. Napoli E, Taroni F, Cortopassi GA (2006) Frataxin, iron-sulfur clusters, heme, ROS, and aging. Antioxid Redox Signal 8(3-4):506-516
16. Bilsland LG, Nirmalananthan N, Yip J, Greensmith L, Duchen MR (2008) Expression of mutant SOD1 in astrocytes induces functional deficits in motoneuron mitochondria. J Neurochem 107(5):1271-1283
17. Casley CS, Land JM, SharpeMA, Clark JB, Duchen MR, Canevari L (2002) Beta-amyloid fragment 25-35 causes mitochondrial dysfunction in primary cortical neurons. Neurobiol Dis 10(3):258-267 (Pubitemid 35217579)
18. Harper ME, Bevilacqua L, Hagopian K, Weindruch R, Ramsey JJ (2004) Ageing, oxidative stress, and mitochondrial uncoupling. Acta Physiol Scand 182(4):321-331 (Pubitemid 39627392)
19. Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS (2004) Characterization of superoxide-producing sites in isolated brain mitochondria. J Biol Chem 279(6):4127-4135 (Pubitemid 38198997)
20. Murphy MP (2009) Mitochondria-A neglected drug target. Curr Opin Investig Drugs 10(10):1022-1024
21. Fukai T, Ushio-Fukai M (2011) Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 15(6):1583-1606
22. Eckert A, Keil U, Marques CA, Bonert A, Frey C, Schåssel K, Måller WE (2003) Mitochondrial dysfunction, apoptotic cell death, and Alzheimer's disease. Biochem Pharmacol 66 (8):1627-1634 (Pubitemid 38373355)
23. Korge P, Ping P, Weiss JN (2008) Reactive oxygen species production in energized cardiac mitochondria during hypoxia/ reoxygenation: modulation by nitric oxide. Circ Res 103 (8):873-880
24. Poyton RO, Ball KA, Castello PR (2009)Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metabol 20(7):332-340
25. Marchetti P, Castedo M, Susin SA, Zamzami N, Hirsch T, Macho A, Haeffner A, Hirsch F, Geuskens M, Kroemer G (1996) Mitochondrial permeability transition is a central coordinating event of apoptosis. J Exp Med 184(3):1155-1160 (Pubitemid 26313572)
26. Martinou JC, Youle RJ (2011) Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 21 (1):92-101
27. Rasola A, Sciacovelli M, Pantic B, Bernardi P (2010) Signal transduction to the permeability transition pore. FEBS Lett 584 (10):1989-1996
28. Reed JC (1998) Bcl-2 family proteins. Oncogene 17(25):3225-3236 (Pubitemid 29043975)
29. Ghatan S, Larner S, Kinoshita Y, Hetman M, Patel L, Xia Z, Youle RJ,Morrison RS (2000) p38 MAP kinasemediates bax translocation in nitric oxide-induced apoptosis in neurons. J Cell Biol 150(2):335-347 (Pubitemid 30491357)
30. An J, Chen Y, Huang Z (2004) Critical upstream signals of cytochrome C release induced by a novel Bcl-2 inhibitor. J Biol Chem 279(18):19133-19140 (Pubitemid 38623344)
31. Hao JH, Yu M, Liu FT, Newland AC, Jia L (2004) Bcl-2 inhibitors sensitize tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by uncoupling of mitochondrial respiration in human leukemic CEM cells. Cancer Res 64(10):3607-3616 (Pubitemid 38657939)
32. Wang JL, Liu D, Zhang ZJ, Shan S, Han X, Srinivasula SM, Croce CM, Alnemri ES, Huang Z (2000) Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci U S A 97(13):7124-7129 (Pubitemid 30431428)
33. Matsuzaki K, Horikiri C (1999) Interactions of amyloid betapeptide (1-40) with ganglioside-containing membranes. Biochemistry 38(13):4137-4142
34. Tamatani M, Ogawa S, Niitsu Y, Tohyama M (1998) Involvement of Bcl-2 family and caspase-3-like protease in NO-mediated neuronal apoptosis. J Neurochem 71(4):1588-1596 (Pubitemid 28443031)
35. Brenner D, Mak TW (2009) Mitochondrial cell death effectors. Curr Opin Cell Biol 21(6):871-877
36. Eilers A, Whitfield J, Vekrellis K, Neame SJ, Shah B, Ham J (1999) c-Jun and Bax: regulators of programmed cell death in developing neurons. Biochem Soc Trans 27(6):790-797 (Pubitemid 30032128)
37. Zhou Q, Lam PY, Han D, Cadenas E (2008) c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. J Neurochem 104(2):325-335 (Pubitemid 350293865)
38. Zhou Q, Lam PY, Han D, Cadenas E (2009) Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging. FEBS Lett 583(7):1132-1140
39. Cory S, Huang DC, Adams JM (2003) The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene 22(53):8590-8607 (Pubitemid 38028528)
40. Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281(5381):1309-1312 (Pubitemid 28406816)
41. Hunter DR, Haworth RA, Southard JH (1976) Relationship between configuration, function, and permeability in calciumtreated mitochondria. J Biol Chem 251(16):5069-5077
42. Azarashvili T, Stricker R, Reiser G (2010) The mitochondria permeability transition pore complex in the brain with interacting proteins-promising targets for protection in neurodegenerative diseases. Biol Chem 391(6):619-629
43. Halestrap AP (2009) What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 46(6):821-831
44. Rodriguez-Enriquez S, He L, Lemasters JJ (2004) Role of mitochondrial permeability transition pores in mitochondrial autophagy. Int J Biochem Cell Biol 36(12):2463-2472 (Pubitemid 39119759)
45. Peixoto PM, Dejean LM, Kinnally KW (2012) The therapeutic potential of mitochondrial channels in cancer, ischemiareperfusion injury, and neurodegeneration. Mitochondrion 12 (1):14-23
46. Zorov DB, Juhaszova M, Yaniv Y, Nuss HB, Wang S, Sollott SJ (2009) Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovasc Res 83(2):213-225
47. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434(7033):658-662 (Pubitemid 40488559)
48. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, Wallace DC (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427(6973):461-465 (Pubitemid 38168501)
49. Baines CP (2007) The mitochondrial permeability transition pore as a target of cardioprotective signaling. Am J Physiol Heart Circ Physiol 293(2):H903-H904 (Pubitemid 47254188)
50. Juhaszova M, Wang S, Zorov DB, Nuss HB, Gleichmann M, Mattson MP, Sollott SJ (2008) The identity and regulation of the mitochondrial permeability transition pore: where the known meets the unknown. Ann N Y Acad Sci 1123:197-212 (Pubitemid 351431318)
51. Zoratti M, Szabo I (1994) Electrophysiology of the inner mitochondrial membrane. J Bioenerg Biomembr 26(5):543-553 (Pubitemid 24378757)
52. McEnery MW (1992) The mitochondrial benzodiazepine receptor: evidence for association with the voltage-dependent anion channel (VDAC). J Bioenerg Biomembr 24(1):63-69
53. Panov A, Dikalov S, Shalbuyeva N, Hemendinger R, Greenamyre JT, Rosenfeld J (2006) Species-and tissue-specific relationships between mitochondrial permeability transition and generation of ROS in brain and liver mitochondria of rats and mice. AJP Cell Physiol 292(2):C708-C718
54. Ricchelli F, Šileikytė J, Bernardi P (2011) Shedding light on the mitochondrial permeability transition. Biochim Biophys Acta (BBA) Bioenerg 1807(5):482-490
55. Colell A (2003) Cholesterol impairs the adenine nucleotide translocator-mediated mitochondrial permeability transition through altered membrane fluidity. J Biol Chem 278(36):33928-33935 (Pubitemid 37553227)
56. Alzheimer's Association (2012) 2012 Alzheimer's disease facts and figures. Alzheimers Dement 8(2):131-168
57. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14(8):837-842
58. Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL (2007) Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci 27(4):796-807 (Pubitemid 46174498)
59. Manczak M, Park BS, Jung Y, Reddy PH (2004) Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med 5(2):147-162 (Pubitemid 38596548)
60. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15(9):1437-1449
61. Valla J, Berndt JD, Gonzalez-Lima F (2001) Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration. J Neurosci 21(13):4923-4930 (Pubitemid 32565651)
62. Schioth HB, Craft S, Brooks SJ, Frey WH, 2nd, Benedict C (2012) Brain insulin signaling and Alzheimer's disease: current evidence and future directions. Mol Neurobiol (in press)
63. Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60(5):748-766
64. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 21(9):3017-3023 (Pubitemid 32323483)
65. Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 29(28):9090-9103
66. Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, Ozmen L, Bluethmann H, Drose S, Brandt U, Savaskan E, Czech C, Gotz J, Eckert A (2009) Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice. Proc Natl Acad Sci U S A 106 (47):20057-20062
67. Keil U, Hauptmann S, Bonert A, Scherping I, Eckert A, Muller WE (2006) Mitochondrial dysfunction induced by disease relevant AbetaPP and tau protein mutations. J Alzheim Dis 9(2):139-146 (Pubitemid 44078641)
68. Leuner K, Schutt T, Kurz C, Eckert SH, Schiller C, Occhipinti A, Mai S, Jendrach M, Eckert GP, Kruse SE, Palmiter RD, Brandt U, Drose S, Wittig I, Willem M, Haass C, Reichert AS, Mueller WE (2012) Mitochondria-derived ROS lead to enhanced amyloid beta formation. Antioxid Redox Signal 16(12):1421-1433
69. Lee HP, Pancholi N, Esposito L, Previll LA, Wang X, Zhu X, Smith MA, Lee HG (2012) Early induction of oxidative stress in mouse model of Alzheimer disease with reduced mitochondrial superoxide dismutase activity. PLoS One 7(1):e28033
70. Schon E, Area-Gomez E (2010) Is Alzheimer's disease a disorder of mitochondria-associated membranes? J Alzheimers Dis JAD 20(Suppl 2):S281-S292
71. Grant SM, Shankar SL, Chalmers-Redman RM, Tatton WG, Szyf M, Cuello AC (1999) Mitochondrial abnormalities in neuroectodermal cells stably expressing human amyloid precursor protein (hAPP751). Neuroreport 10(1):41-46 (Pubitemid 29090475)
72. Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG (2003) Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol 161 (1):41-54 (Pubitemid 36459078)
73. Keil U, Bonert A, Marques CA, Scherping I, Weyermann J, Strosznajder JB, Muller-Spahn F, Haass C, Czech C, Pradier L, Muller WE, Eckert A (2004) Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol Chem 279(48):50310-50320 (Pubitemid 39577847)
74. Hansson CA, Frykman S, Farmery MR, Tjernberg LO, Nilsberth C, Pursglove SE, Ito A, Winblad B, Cowburn RF, Thyberg J, Ankarcrona M (2004) Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria. J Biol Chem 279(49):51654-51660 (Pubitemid 40017916)
75. Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS (2010) Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A 107(43):18670-18675
76. Pagani L, Eckert A (2011) Amyloid-Beta interaction with mitochondria. Int J Alzheimers Dis 2011:925050
77. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 304(5669):448-452 (Pubitemid 38495942)
78. Lustbader JW (2004) ABAD directly links a to mitochondrial toxicity in Alzheimer's disease. Science 304(5669):448-452 (Pubitemid 38495942)
79. Borger E, Aitken L, Muirhead KE, Allen ZE, Ainge JA, Conway SJ, Gunn-Moore FJ (2011) Mitochondrial beta-amyloid in Alzheimer's disease. Biochem Soc Trans 39(4):868-873
80. Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Du Yan S (2008) Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 14(10):1097-1105
81. Du H, Yan S (2010) Mitochondrial permeability transition pore in Alzheimer's disease: cyclophilin D and amyloid beta. Biochim Biophys Acta 1802(1):198-204
82. Du H,Guo L, ZhangW, RydzewskaM,Yan S (2011) Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiol Aging 32 (3):398-406
83. Heales SJ, Bolanos JP, Stewart VC, Brookes PS, Land JM, Clark JB (1999) Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1410(2):215-228 (Pubitemid 29078606)
84. Brookes PS (2004) Mitochondrial nitric oxide synthase. Mitochondrion 3(4):187-204 (Pubitemid 38263634)
85. Ban JY, Cho SO, Koh SB, Song KS, Bae K, Seong YH (2006) Protection of amyloid beta protein (25-35)-induced neurotoxicity by methanol extract of Smilacis chinae rhizome in cultured rat cortical neurons. J Ethnopharmacol 106(2):230-237 (Pubitemid 43766192)
86. Colton CA, Vitek MP, Wink DA, Xu Q, Cantillana V, Previti ML, Van Nostrand WE, Weinberg JB, Dawson H (2006) NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 103(34):12867-12872 (Pubitemid 44298653)
87. Chopra K, Misra S, Kuhad A (2011) Current perspectives on pharmacotherapy of Alzheimer's disease. Expert Opin Pharmacother 12(3):335-350
88. Reddy PH, Tripathi R, Troung Q, Tirumala K, Reddy TP, Anekonda V, Shirendeb UP, Calkins MJ, Reddy AP, Mao P, Manczak M (2012) Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: implications to mitochondria-targeted antioxidant therapeutics. Biochim Biophys Acta 1822(5):639-649
89. Schaffer S, Asseburg H, Kuntz S, Muller WE, Eckert GP (2012) Effect of polyphenols on brain aging and Alzheimer's disease: focus on mitochondria. Mol Neurobiol (in press)
90. Sachdeva D, Burns A (2011) Dimebolin in dementia. CNS Neurosci Ther 17(3):199-205
91. Bachurin S, Bukatina E, Lermontova N, Tkachenko S, Afanasiev A, Grigoriev V, Grigorieva I, Ivanov Y, Sablin S, Zefirov N (2001) Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer. Ann N Y Acad Sci 939:425-435 (Pubitemid 32620096)
92. Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO, Seely L, Hung D (2008) 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. Lancet 372 (9634):207-215 (Pubitemid 351978110)
93. Kieburtz K, McDermott MP, Voss TS, Corey-Bloom J, Deuel LM, Dorsey ER, Factor S, Geschwind MD, Hodgeman K, Kayson E, Noonberg S, Pourfar M, Rabinowitz K, Ravina B, Sanchez-Ramos J, Seely L, Walker F, Feigin A (2010) A randomized, placebo-controlled trial of latrepirdine in Huntington disease. Arch Neurol 67(2):154-160
94. Vignisse J, Steinbusch HW, Bolkunov A, Nunes J, Santos AI, Grandfils C, Bachurin S, Strekalova T (2011) Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice. Prog Neuropsychopharmacol Biol Psychiatry 35(2):510-522
95. Wang J, Ferruzzi MG, Varghese M, Qian X, Cheng A, Xie M, Zhao W, Ho L, Pasinetti GM (2011) Preclinical study of Dimebon on beta-amyloid-mediated neuropathology in Alzheimer's disease. Mol Neurodegener 6(1):7
96. Giorgetti M, Gibbons JA, Bernales S, Alfaro IE, Drieu LR, Cremers T, Altar CA, Wronski R, Hutter-Paier B, Protter AA (2010) Cognition-enhancing properties of Dimebon in a rat novel object recognition task are unlikely to be associated with acetylcholinesterase inhibition or N-methyl-D-aspartate receptor antagonism. J Pharmacol Exp Ther 333(3):748-757
97. Schaffhauser H, Mathiasen JR, Dicamillo A, Huffman MJ, Lu LD, McKenna BA, Qian J, Marino MJ (2009) Dimebolin is a 5-HT6 antagonist with acute cognition enhancing activities. Biochem Pharmacol 78(8):1035-1042
98. Webster SJ, Wilson CA, Lee CH, Mohler EG, Terry AV Jr, Buccafusco JJ (2011) The acute effects of dimebolin, a potentialAlzheimer's disease treatment, on working memory in rhesus monkeys. Br J Pharmacol 164(3):970-978
99. Jimeson M, Machado P (2010) Pfizer and medivation announce results from two phase 3 studies in Dimebon (latrepirdine.) Alzheimer's disease clinical development program. http://investors.medivation.com/releasedetail.cfm? releaseid0448818. Accessed 10 Feb 12
100. Su B, Wang X, Bonda D, Perry G, Smith M, Zhu X (2010) Abnormal mitochondrial dynamics-A novel therapeutic target for Alzheimer's disease? Mol Neurobiol 41(2-3):87-96
101. Moreira PI, Zhu X,Wang X, Lee HG, Nunomura A, Petersen RB, Perry G, Smith MA (2010) Mitochondria: A therapeutic target in neurodegeneration. Biochim Biophys Acta 1802(1):212-220
102. Reddy PH (2009) Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease. Exp Neurol 218 (2):286-292
103. Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol Med 14(2):45-53
104. Lermontova NN, Redkozubov AE, Shevtsova EF, Serkova TP, Kireeva EG, Bachurin SO (2001) Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca (2+) channels. Bull Exp Biol Med 132(5):1079-1083 (Pubitemid 34295938)
105. Wu J, Li Q, Bezprozvanny I (2008) Evaluation of Dimebon in cellular model of Huntington's disease. Mol Neurodegener 3:15
106. Zhang S, Hedskog L, Petersen CA, Winblad B, Ankarcrona M (2010) Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death. J Alzheim Dis 21(2):389-402
107. Eckert SH, Eckmann J, Renner K, Eckert GP, Leuner K, Muller WE (2012) Dimebon ameliorates amyloid-β induced impairments of mitochondrial form and function. J Alzheim Dis (in press)
108. Kupfer A, Aeschlimann C, Wermuth B, Cerny T (1994) Prophylaxis and reversal of ifosfamide encephalopathy with methyleneblue. Lancet 343(8900):763-764 (Pubitemid 24098694)
109. Clifton J 2nd, Leikin JB (2003) Methylene blue. Am J Ther 10 (4):289-291
110. Oz M, Isaev D, Lorke DE, Hasan M, Petroianu G, Shippenberg TS (2012) Methylene blue inhibits function of the 5-HT transporter. Br J Pharmacol 166(1):168-176
111. Naylor GJ, Smith AH, Connelly P (1988) Methylene blue in mania. Biol Psychiatry 24(8):941-942 (Pubitemid 19004170)
112. de Oliveira RW, Del Bel EA, Guimaraes FS (2000) Behavioral and c-fos expression changes induced by nitric oxide donors microinjected into the dorsal periaqueductal gray. Brain Res Bull 51(6):457-464 (Pubitemid 30176088)
113. de-Oliveira RW, Guimaraes FS (1999) Anxiolytic effect of methylene blue microinjected into the dorsal periaqueductal gray matter. Braz J Med Biol Res 32(12):1529-1532 (Pubitemid 30053339)
114. Rengelshausen J, Burhenne J, Frohlich M, Tayrouz Y, Singh SK, Riedel KD, Muller O, Hoppe-Tichy T, Haefeli WE, Mikus G, Walter-Sack I (2004) Pharmacokinetic interaction of chloroquine and methylene blue combination against malaria. Eur J Clin Pharmacol 60(10):709-715
115. Peter C, Hongwan D, Kupfer A, Lauterburg BH (2000) Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol 56(3):247-250 (Pubitemid 30456685)
116. Lindahl PE, Oberg KE (1961) The effect of rotenone on respiration and its point of attack. Exp Cell Res 23:228-237
117. Riha PD, Bruchey AK, Echevarria DJ, Gonzalez-Lima F (2005) Memory facilitation by methylene blue: Dose-dependent effect on behavior and brain oxygen consumption. Eur J Pharmacol 511(2-3):151-158 (Pubitemid 40417721)
118. Martinez JL, Jensen RA, Vasquez B, McGuinness G, McGaugh JL (1978) Methylene blue alters retention of inhibitory avoidance responses. Physiol Pschol 6:387-390
119. Callaway NL, Riha PD, Bruchey AK, Munshi Z, Gonzalez-Lima F (2004) Methylene blue improves brain oxidative metabolism and memory retention in rats. Pharmacol Biochem Behav 77 (1):175-181 (Pubitemid 38076994)
120. Gonzalez-Lima F, Valla J, Matos-Collazo S (1997) Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients. Brain Res 752(1-2):117-126 (Pubitemid 27143904)
121. Hauptmann S, Scherping I, Drose S, Schulz KL, Jendrach M, Brandt U, Leuner K, Eckert A, Mueller WE (2007) Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with aging. Neurobiol Aging 30(10):1574-1586
122. Zhang X, Rojas JC, Gonzalez-Lima F (2006) Methylene blue prevents neurodegeneration caused by rotenone in the retina. Neurotox Res 9(1):47-57
123. Leuner K, Hauptmann S, Abdel-Kader R, Scherping I, Keil U, Strosznajder JB, Eckert A, Muller WE (2007) Mitochondrial dysfunction: the first domino in brain aging and Alzheimer's disease? Antioxid Redox Signal 9(10):1659-1675 (Pubitemid 47462969)
124. Deiana S, Harrington CR, Wischik CM, Riedel G (2009) Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine. Psychopharmacology (Berl) 202(1-3):53-65
125. Reddy PH, Reddy TP (2011) Mitochondria as a therapeutic target for aging and neurodegenerative diseases. Curr Alzheimer Res 8 (4):393-409
126. Salaris SC, Babbs CF, Voorhees WD 3rd (1991) Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury. Biochem Pharmacol 42(3):499-506
127. Riedel W, Lang U, Oetjen U, Schlapp U, Shibata M (2003) Inhibition of oxygen radical formation by methylene blue, aspirin, or alpha-lipoic acid, prevents bacterial-lipopolysaccharide-induced fever. Mol Cell Biochem 247(1-2):83-94 (Pubitemid 36798512)
128. Visarius TM, Stucki JW, Lauterburg BH (1997) Stimulation of respiration by methylene blue in rat liver mitochondria. FEBS Lett 412(1):157-160 (Pubitemid 27310021)
129. Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN (2008) Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. FASEB J 22 (3):703-712 (Pubitemid 351348123)
130. Wischik CM, Edwards PC, Lai RY, RothM, Harrington CR (1996) Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A 93(20):11213-11218 (Pubitemid 26333144)
131. Medina DX, Caccamo A, Oddo S (2011) Methylene blue reduces abeta levels and rescues early cognitive deficit by increasing proteasome activity. Brain Pathol 21(2):140-149
132. Mayer B, Brunner F, Schmidt K (1993) Novel actions of methylene blue. Eur Heart J 14(Suppl I):22-26 (Pubitemid 23362589)
133. Parri HR, Hernandez CM, Dineley KT (2011) Research update: Alpha7 nicotinic acetylcholine receptor mechanisms in Alzheimer's disease. Biochem Pharmacol 82(8):931-942
134. Al Mansouri AS, Lorke DE, Nurulain SM, Ashor A, Keun-Hang SY, Petroianu G, Isaev D, Oz M (2012) Methylene blue inhibits the function of alpha7-nicotinic acetylcholine receptors. CNS Neurol Disord Drug Targets (in press)
135. Muller WE, Eckert GP, Eckert A (1999) Piracetam: novelty in a unique mode of action. Pharmacopsychiatry 32(Suppl 1):2-9
136. Winblad B (2005) Piracetam: A review of pharmacological properties and clinical uses. CNS Drug Rev 11(2):169-182 (Pubitemid 41278980)
137. Waegemans T, Wilsher CR, Danniau A, Ferris SH, Kurz A, Winblad B (2002) Clinical efficacy of Piracetam in cognitive impairment: A meta-analysis. Dement Geriatr Cogn Disord 13 (4):217-224 (Pubitemid 34507607)
138. Dormehl IC, Jordaan B, Oliver DW, Croft S (1999) SPECT monitoring of improved cerebral blood flow during long-term treatment of elderly patients with nootropic drugs. Clin Nucl Med 24(1):29-34 (Pubitemid 29024658)
139. Domanska-Janik K, Zaleska M (1977) The action of Piracetam on 14C-glucose metabolism in normal and posthypoxic rat cerebral cortex slices. Pol J Pharmacol Pharm 29(2):111-116 (Pubitemid 8096076)
140. Heiss WD, Hebold I, Klinkhammer P, Ziffling P, Szelies B, Pawlik G, Herholz K (1988) Effect of Piracetam on cerebral glucose metabolism in Alzheimer's disease as measured by positron emission tomography. J Cerebr Blood Flow Metabol Off J Int Soc Cereb Blood Flow Metab 8(4):613-617
141. Eckert GP, Cairns NJ, Muller WE (1999) Piracetam reverses hippocampal membrane alterations in Alzheimer's disease. J Neural Transm 106(7-8):757-761 (Pubitemid 29401363)
142. Keil U, Scherping I, Hauptmann S, Eckert A, Muller WE (2005) Stabilization of mitochondrial function by Piracetam. Pharmacopsychiatry 38(5):253-253
143. Kurz C, Ungerer I, Lipka U, Kirr S, Schutt T, Eckert A, Leuner K, Muller WE (2010) The metabolic enhancer Piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide. Br J Pharmacol 160(2):246-257
144. Leuner K, Kurz C, Guidetti G, Orgogozo JM, Muller WE (2010) Improved mitochondrial function in brain aging and Alzheimer disease-The new mechanism of action of the old metabolic enhancer Piracetam. Front Neurosci 4:pii 44
145. Ricchelli F, Gobbo S, Moreno G, Salet C (1999) Changes of the fluidity of mitochondrial membranes induced by the permeability transition. Biochemistry 38(29):9295-9300
146. Muriel P, Perez-Rojas JM (2003) Nitric oxide inhibits mitochondrial monoamine oxidase activity and decreases outer mitochondria membrane fluidity. Comp Biochem Physiol Toxicol Pharmacol CBP 136(3):191-197 (Pubitemid 37500848)
147. Aleardi AM, Benard G, Augereau O, Malgat M, Talbot JC, Mazat JP, Letellier T, Chary-Prigent J, Solaini GC, Rossignol R (2005) Gradual alteration of mitochondrial structure and function by beta-amyloids: importance of membrane viscosity changes, energy deprivation, reactive oxygen species production, and cytochrome c release. J Bioenerg Biomembr 37(4):207-225 (Pubitemid 41420458)
148. Lennernas H, Fager G (1997) Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin Pharmacokinet 32(5):403-425 (Pubitemid 27199232)
149. Wood WG, Eckert GP, Igbavboa U, Muller WE (2010) Statins and neuroprotection: A prescription to move the field forward. Ann N Y Acad Sci 1199:69-76
150. Eckert GP, Wood WG, Muller WE (2005) Statins: Drugs for Alzheimer's disease? J Neural Transm 112(8):1057-1071 (Pubitemid 40991521)
151. McGuinness B, O'Hare J, Craig D, Bullock R, Malouf R, Passmore P (2010) Statins for the treatment of dementia. Cochrane Database Syst Rev (8):CD007514
152. Li L, Cao D, Kim H, Lester R, Fukuchi K (2006) Simvastatin enhances learning and memory independent of amyloid load in mice. Ann Neurol 60(6):729-739 (Pubitemid 46061359)
153. Tong XK, Nicolakakis N, Fernandes P, Ongali B, Brouillette J, Quirion R, Hamel E (2009) Simvastatin improves cerebrovascular function and counters
154. Tong XK, Lecrux C, Hamel E (2012) Age-dependent rescue by simvastatin of Alzheimer's disease cerebrovascular and memory deficits. J Neurosci 32(14):4705-4715
155. Eckert GP, Hooff GP, Strandjord DM, Igbavboa U, Volmer DA, Muller WE, Wood WG (2009) Regulation of the brain isoprenoids farnesyl-and geranylgeranylpyrophosphate is altered in male Alzheimer patients. Neurobiol Dis 35(2):251-257
156. Hooff GP,Wood WG, Muller WE, Eckert GP (2010) Isoprenoids, small GTPases and Alzheimer's disease. Biochim Biophys Acta 1801(8):896-905
157. Li L, Zhang W, Cheng S, Cao D, Parent M (2012) Isoprenoids and related pharmacological interventions: potential application in Alzheimer's disease. Mol Neurobiol (in press)
158. Johnson-Anuna LN, Eckert GP, Keller JH, Igbavboa U, Franke C, Fechner T, Schubert-Zsilavecz M, Karas M, Måller WM, Wood WG (2005) Chronic administration of statins alters multiple gene expression patterns in mouse cerebral cortex. J Pharmacol Exp Ther 312(2):786-793 (Pubitemid 40189580)
159. Johnson-Anuna LN, Eckert GP, Franke C, Igbavboa U, Muller WE, WoodWG(2007) Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein. J Neurochem 101(1):77-86 (Pubitemid 46426484)
160. Butterick TA, Igbavboa U, Eckert GP, Sun GY, Weisman GA, Muller WE, Wood WG (2010) Simvastatin stimulates production of the antiapoptotic protein Bcl-2 via endothelin-1 and NFATc3 in SH-SY5Y cells. Mol Neurobiol 41(2-3):384-391
161. Franke C, NoldnerM, Abdel-Kader R, Johnson-Anuna LN, Gibson WW, Muller WE, Eckert GP (2007) Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment. Neurobiol Dis 25(2):438-445 (Pubitemid 46138047)
162. Zamzami N, Marchetti P, Castedo M, Hirsch T, Susin SA, Masse B, Kroemer G (1996) Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis. FEBS Lett 384(1):53-57 (Pubitemid 26114720)
163. Shimizu S, Eguchi Y, KamiikeW,Waguri S, Uchiyama Y, Matsuda H, Tsujimoto Y (1996) Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of death induced by respiratory chain inhibitors. Oncogene 13(1):21-29 (Pubitemid 26248541)
164. Patassini S, Giampa C, Martorana A, Bernardi G, Fusco FR (2008) Effects of simvastatin on neuroprotection and modulation of Bcl-2 and BAX in the rat quinolinic acid model of Huntington's disease. Neurosci Lett 448(1):166-169
165. Ko ML, Chen CF, Peng PH, Peng YH (2011) Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina. Exp Eye Res 93 (5):580-585
166. Sastre J, Lloret A, Borras C, Pereda J, Garcia-Sala D, Droy-Lefaix MT, Pallardo FV, Vina J (2002) Ginkgo biloba extract EGb 761 protects against mitochondrial aging in the brain and in the liver. Cell Mol Biol (Noisy-le-grand) 48(6):685-692
167. Abdel-Kader RM, Hauptmann S, Keil U, Scherping I, Leuner K, Eckert A, Muller WE (2007) Stabilization of mitochondrial function by Ginkgo biloba extract (EGb 761). Pharmacol Res 56 (6):493-502 (Pubitemid 350148165)
168. Bedir E, Tatli II, Khan RA, Zhao J, Takamatsu S, Walker LA, Goldman P, Khan IA (2002) Biologically active secondary metabolites from Ginkgo biloba. J Agric Food Chem 50 (11):3150-3155 (Pubitemid 34533615)
169. Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN (2010) Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr 10:14
170. Wang BS, Wang H, Song YY, Qi H, Rong ZX, Zhang L, Chen HZ (2010) Effectiveness of standardized Ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: A bivariate random effect meta-analysis. Pharmacopsychiatry 43 (3):86-91
171. Ihl R, Frolich L, Winblad B, Schneider L, Burns A, Moller HJ (2011) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of Alzheimer's disease and other dementias. World J Biol Psychiatr Off J World Fed Soc Biol Psychiatry 12(1):2-32
172. DeKosky ST, Williamson JD, Fitzpatrick AL, Kronmal RA, Ives DG, Saxton JA, Lopez OL, Burke G, Carlson MC, Fried LP, Kuller LH, Robbins JA, Tracy RP, Woolard NF, Dunn L, Snitz BE, Nahin RL, Furberg CD (2008) Ginkgo biloba for prevention of dementia: A randomized controlled trial. Jama 300(19):2253-2262
173. Vellas B, Coley N, Ousset P-J, Berrut G, Dartigues J-F, Dubois B, Grandjean H, Pasquire F, Piette G, Robert P, Touchon J, Garnier P, Mathiex-Fortunet H, Andrieu S (2010) Results of GUIDEAGE-A 5-year placebo-controlled study on the efficacy of EGb761 120 mg to prevent or delay Alzheimer's dementia onset in elderly subjects with memory copmlaint. J Nutr Health Aging 14(Supp 2):S23
174. Fehske CJ, Leuner K, Muller WE (2009) Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment. Pharmacol Res Off J Ital Pharmacol Soc 60(1):68-73
175. Eckert A, Keil U, Scherping I, Hauptmann S, Muller WE (2005) Stabilization of mitochondrial membrane potential and improvement of neuronal energy metabolism by Ginkgo biloba extract EGb 761. Ann New York Acad Sci 1056:474-485 (Pubitemid 43031000)
176. Schindowski K, Leutner S, Kressmann S, Eckert A, Muller WE (2001) Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761). J Neural Transm 108(8-9):969-978 (Pubitemid 32802094)
177. Abdel-Kader RM, Scherping I, Hauptmann S, Keil U, Muller WE (2006) Protective effects of Ginkgo biloba extract in different animal models. Naunyn-Schmiedeberg's Arch Exp Pathol Pharmakol 372(Supplement 1):294
178. Muller WE, Heiser J, Leuner K (2012) Effects of standardized Ginkgo biloba extract EGb 761 on neuroplasticity. Int Psychogeriatr (in press)
179. Colciaghi F, Borroni B, Zimmermann M, Bellone C, Longhi A, Padovani A, Cattabeni F, Christen Y, Di Luca M (2004) Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts. Neurobiol Dis 16(2):454-460 (Pubitemid 38757325)
180. Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ, Buford JP, Khan I, Netzer WJ, Xu H, Butko P (2002) Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Nat Acad Sci 99(19):12197-12202
181. Stoll S, Scheuer K, Pohl O, Muller WE (1996) Ginkgo biloba extract (EGb 761) independently improves changes in passive avoidance learning and brain membrane fluidity in the aging mouse. Pharmacopsychiatry 29(4):144-149 (Pubitemid 26247564)
182. Tang F, Nag S, Shiu SY, Pang SF (2002) The effects of melatonin and Ginkgo biloba extract on memory loss and choline acetyltransferase activities in the brain of rats infused intracerebroventricularly with beta-amyloid 1-40. Life Sci 71(22):2625-2631 (Pubitemid 35279305)
183. Luo C, Wu Q, Huang XN, Sun AS, Shi JS (2003) Ginkgo biloba leaf extract enhances levels of caspase-3 and amyloid precursor protein in normal rat hippocampus. Acta Pharmacol Sin 24 (2):152-156 (Pubitemid 36168363)
184. Garcia-Alloza M, Dodwell SA, Meyer-Luehmann M, Hyman BT, Bacskai BJ (2006) Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model. J Neuropathol Exp Neurol 65(11):1082-1089 (Pubitemid 44684666)
185. Stackman RW, Eckenstein F, Frei B, Kulhanek D, Nowlin J, Quinn JF (2003) Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment. Exp Neurol 184(1):510-520 (Pubitemid 37444058)
186. Sikora E, Bielak-Zmijewska A, Mosieniak G, Piwocka K (2010) The promise of slow down ageing may come from curcumin. Curr Pharm Des 16(7):884-892
187. Lapchak PA (2011) Neuroprotective and neurotrophic curcuminoids to treat stroke: A translational perspective. Expet Opin Investig Drugs 20(1):13-22
188. Scapagnini G, Caruso C, Calabrese V (2011) Therapeutic potential of dietary polyphenols against brain ageing and neurodegenerative disorders. Adv Exp Med Biol 698:27-35
189. Zhu YG, Chen XC, Chen ZZ, Zeng YQ, Shi GB, Su YH, Peng X (2004) Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons. Acta Pharmacol Sin 25(12):1606-1612 (Pubitemid 39628027)
190. Bengmark S (2006) Impact of nutrition on ageing and disease. Curr Opin Clin Nutr Metab Care 9(1):2-7 (Pubitemid 44124212)
191. Raza H, John A, Brown EM, Benedict S, Kambal A (2008) Alterations inmitochondrial respiratory functions, redoxmetabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells. Toxicol Appl Pharmacol 226(2):161-168
192. Ataie A, Sabetkasaei M, Haghparast A, Moghaddam AH, Kazeminejad B (2010) Neuroprotective effects of the polyphenolic antioxidant agent, curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat. Pharmacol Biochem Behav 96(4):378-385
193. Dkhar P, Sharma R (2010) Effect of dimethylsulphoxide and curcumin on protein carbonyls and reactive oxygen species of cerebral hemispheres of mice as a function of age. Int J Dev Neurosci 28(5):351-357
194. Kumar A, Prakash A, Dogra S (2011) Protective effect of curcumin (Curcuma longa) against D-galactose-induced senescence in mice. J Asian Nat Prod Res 13(1):42-55
195. Rastogi M, Ojha RP, Rajamanickam GV, Agrawal A, Aggarwal A, Dubey GP (2008) Curcuminoids modulates oxidative damage and mitochondrial dysfunction in diabetic rat brain. Free Radic Res 42(11-12):999-1005
196. Izem-Meziane M, Djerdjouri B, Rimbaud S, Caffin F, Fortin D, Garnier A, Veksler V, Joubert F, Ventura-Clapier R (2012) Catecholamine-induced cardiac mitochondrial dysfunction and mPTP opening: protective effect of curcumin. Am J Physiol Heart Circ Physiol 302(3):H665-H674
197. Hamaguchi T, Ono K, Yamada M (2010) Curcumin and Alzheimer's disease. CNS Neurosci Ther 16(5):285-297
198. Belkacemi A, Doggui S, Dao L, Ramassamy C (2011) Challenges associated with curcumin therapy in Alzheimer disease. Expert Rev Mol Med 13:e34
199. Cole GM, Ma QL, Frautschy SA (2009) Omega-3 fatty acids and dementia. Prostaglandins Leukot Essent Fat Acids 81(2-3):213-221
200. Eckert GP, Chang S, Eckmann J, Copanaki E, Hagl S, Hener U, Muller WE, Kogel D (2011) Liposome-incorporated DHA increases neuronal survival by enhancing non-amyloidogenic APP processing. Biochim Biophys Acta 1808(1):236-243
201. Stanley WC, Khairallah RJ, Dabkowski ER (2012) Update on lipids and mitochondrial function: impact of dietary n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 15(2):122-126
202. Atamna H, Frey WH (2007) Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion 7(5):297-310 (Pubitemid 47300175)
203. Benzi G, Pastoris O, Marzatico F, Villa RF, Dagani F, Curti D (1992) The mitochondrial electron transfer alteration as a factor involved in the brain aging. Neurobiol Aging 13(3):361-368
204. Lenaz G, Bovina C, Castelluccio C, Fato R, Formiggini G, Genova ML, Marchetti M, Pich MM, Pallotti F, Parenti CG, Biagini G (1997) Mitochondrial complex I defects in aging. Mol Cell Biochem 174(1-2):329-333 (Pubitemid 27404210)
205. MartinezM, FerrandizML, De Juan E,Miquel J (1994) Age-related changes in glutathione and lipid peroxide content in mouse synaptic mitochondria: relationship to cytochrome c oxidase decline. Neurosci Lett 170(1):121-124 (Pubitemid 24117302)
206. Leutner S, Eckert A, Mueller WE (2001) ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain. J Neural Transm 108(8-9):955-967 (Pubitemid 32802093)
207. Eckert GP, Franke C, Noldner M, Rau O, Wurglics M, Schubert-Zsilavecz M, Muller WE (2010) Plant derived omega-3-fatty acids protect mitochondrial function in the brain. Pharmacol Res 61(3):234-241
208. Barcelo-Coblijn G, Kitajka K, Puskas LG, Hogyes E, Zvara A, Hackler L Jr, Farkas T (2003) Gene expression and molecular composition of phospholipids in rat brain in relation to dietary n-6 to n-3 fatty acid ratio. Biochim Biophys Acta 1632(1-3):72-79 (Pubitemid 36628118)
209. Umezawa M, Kogishi K, Tojo H, Yoshimura S, Seriu N, Ohta A, Takeda T, Hosokawa M (1999) High-linoleate and high-alpha-linolenate diets affect learning ability and natural behavior in SAMR1 mice. J Nutr 129(2):431-437 (Pubitemid 29072132)
210. Okaniwa Y, Yuasa S, Yamamoto N, Watanabe S, Kobayashi T, Okuyama H, Nomura M, Nagata Y (1996) A high linoleate and a high alpha-linolenate diet induced changes in learning behavior of rats. Effects of a shift in diets and reversal of training stimuli. Biol Pharm Bull 19(4):536-540 (Pubitemid 26144610)