Mitochondrial Involvement in Brain Function and Dysfunction: Relevance to Aging, Neurodegenerative Disorders and Longevity
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It is becoming increasingly evident that the mitochondrial genome may play a key role in neurodegenerative diseases. Mitochondrial dysfunction is characteristic of several neurodegenerative disorders, and evidence for mitochondria being a site of damage in neurodegenerative disorders is partially based on decreases in respiratory chain complex activities in Parkinson's disease, Alzheimer's disease, and Huntington's disease. Such defects in respiratory complex activities, possibly associated with oxidant/antioxidant balance perturbation, are thought to underlie defects in energy metabolism and induce cellular degeneration. Efficient functioning of maintenance and repair process seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of genes termed vitagenes. A promising approach for the identification of critical gerontogenic processes is represented by the hormesis-like positive effect of stress. In the present review, we discuss the role of energy thresholds in brain mitochondria and their implications in neurodegeneration. We then review the evidence for the role of oxidative stress in modulating the effects of mitochondrial DNA mutations on brain age-related disorders and also discuss new approaches for investigating the mechanisms of lifetime survival and longevity.
Stewart, V. C., Sharpe, M. A., Clark, J. B., and Heales, S. J. 2000. Astrocyte-derived nitric oxide causes both reversible and irreversible damage to the neuronal mitochondrial respiratory chain. J. Neurochem. 75:694–700.
Halliwell, B. 1999. Antioxidant defence mechanisms: From the beginning to the end (of the beginning). Free Radic. Res. 31:261–272.
Calabrese, V., Bates, T. E., and Giuffrida Stella, A. M. 2000. NO synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders: The role of oxidant/antioxidant balance. Neurochem. Res. 25:1315–1341.
Morimoto, R. I. and Santoro, M. G. 1998. Stress-inducible response and heat shock proteins: New pharmacologic targets for cytoprotection. Nature Biotechnol. 16:833–838.
Calabrese, V., Testa, D., Ravagna, A., Bates, T. E., and Giuffrida Stella, A. M. 2000. HSP70 induction in the brain following ethanol administration in the rat: Regulation by glutathione redox state. Biochem. Biophys. Res. Comm. 269:397–400.
Calabrese, V., Copani, A., Testa, D., Ravagna, A., Spadaro, F., Tendi, E., Nicoletti, V. G., and Giuffrida Stella, A. M. 2000. Nitric oxide synthase induction in astroglial cell cultures: Effect on heat shock protein 70 synthesis and oxidant/antioxidant balance. J. Neurosci. Res. 60:613–622.
Motterlini, R., Foresti, R., Bassi, R., Calabrese, V., Clark, J. E., and Green, C. J. 2000. Endothelial Heme oxygenase-1 induction by hypoxia: Modulation by inducible nitric oxide synthase (iNOS) and S-nitrosothiols. J. Biol. Chem. 275:13613–13620.
Harman, D. 1972. Free radical theory of ageing: Dietary implications. Am. J. Clin. Nutr. 25:839–843.
Beckman, K. B. and Ames, B. N. 1998. Mitochondrial aging: Open questions. Ann. NY Acad. Sci. 854:118–127.
McHenry, L. C., Merory, J., Bass, E., Stump, D. A., Williams, R., Witcofski, R., Howard, G., and Toole, J. F. 1978. Xenon-133 inhalation method for regional cerebral blood flow measurements: Normal values and test-retest results. Stroke 9:396–399.
Ginsberg, M. D., Sternau, L. L., Globus, M. Y., Dietrich, W. D., and Busto, R. 1992. Therapeutic modulation of brain temperature: Relevance to ischemic brain injury. Cerebrovasc. Brain Metab. Rev. 4:189–225.
Altmann, B. 1894. Cited in: E. de Robertis, W. Nowinski, F. Saez (eds.), Cell Biology, W. B. Saunders, Philadelphia, 1970, pp 199–228.
Nass, S. and Nass, M. M. 1963. Intramitochondrial fibers and DNA Characteristics: II. Enzymatic and other hydrolytic treatments. J. Cell. Biol. 19:613–629.
Dujon, B. 1981. Mitochondrial genetics and functions. In: Strathern, J. N., Jones, E. W., Broach, J. R. (eds.), Molecular Biology of the yeast Saccharomyces; Life cycle, and inheritance. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 505–635.
Shadel, G. S. and Clayton, D. A. 1997. Mitochondrial DNA maintenance in vertebrates. Annu. Rev. Biochem. 66:409–435.
Jang, S. H. and Jaehning, J. A. 1991. The yeast mitochondrial RNA polymerase specificity factor, MTF1, is similar to bacterial sigma factors. J. Biol. Chem. 266:22671–22677.
Scacco, S., Vergari, R., Scarpulla, R. C., Technikova-Dobrova, Z., Sardanelli, A., Lambo, R., Lorusso, V., and Papa, S. 2000. cAMP-dependent phosphorylation of the nuclear encoded 18-kDa (IP) subunit of respiratory complex I and activation of the complex in serum-starved mouse fibroblast cultures. J. Biol. Chem. 275:17578–17582.
Herzig, R. P., Scacco, S., and Scarpulla, R. C. 2000. Sequential serum-dependent activation of CREB and NRF-1 leads to enhanced mitochondrial respiration through the induction of cytochrome c. J. Biol. Chem. 275:13134–13141.
Richter C. and Schweizer M. 1997. Oxidative stress in mitochondria. In Oxidative stress and the molecular biology of antioxidant defenses. Scandalios J. G., Cold Spring Harbor Laboratory Press. Planview, NY.
Swerdlow, R. H., Parks, J. K., Cassarino, D. S., Maguire, D. J., Maguire, R. S., Bennett, J. P., Davis, R. E., and Parker, W. D. 1997. Cybrids in Alzheimer disease: A cellular model of the disease? Neurology 49:918–925.
Luft, R., Ikkos, D., Palmieri, G., Ernster, L., and Afzelius, A. 1962. A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: A correlated clinical, biochemical and morphological study. J. Clin. Invest. 41:1776–1804.
Cottrell, D. A. and Turnbull, D. M. 2000. Mitochondria and ageing. Curr. Opin. Clin. Nutr. Metab. Care 3:473–478.
Wallace, D. C. 1999. Mitochondrial diseases in man and mouse. Science 283:1482–1488.
Chomyn, A., Martinuzzi, A., Yoneda, M., Daga, A., Hurko, O., Johns, D., Lai, S. T., Nonaka, I., Angelini, C., and Attardi, G. 1992. MELAS mutations in mtDNA site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts. Proc. Natl. Acad. Sci. USA 89:4221–4225.
Mazat, J., Rossignol, R., Malgat, M., Rocher, C., Faustin, B., and Letellier, T. 2001. What do mitochondrial diseases teach us about normal mitochondrial functions that we already knew: Threshold expression of mitochondrial defects. Biochim. Biophys. Acta 1504:20–30.
Letellier, T., Malgat, M., Rossignol, R., and Mazat, J. P. 1998. Metabolic control analysis and mitochondrial pathologies. Mol. Cell. Biochem. 184:409–417.
Davey, G. P., Peuchen, S., and Clark, J. B. 1998. Energy thresholds in brain mitochondria. J. Biol. Chem. 273:12753–12757.
Malgat, M., Latellier, T., Jouaville, S. L., and Mazat, J. 1995. Value of control theory in the study of cellular metabolism. Biomedical implications. J. Biol. Systems 3:165–175.
Rossignol, R., Letellier, T., Malgat, M., Rocher, C., and Mazat, J. P. 2000. Tissue variation in the control of oxidative phosphorylation: Implication for mitochondrial diseases. Biochem. J. 347:45–53.
Rossignol, R., Malgat, M., Mazat, J. P., and Letellier, T. 1999. Threshold effect and tissue specificity. Implication for mitochondrial cytopathies. J. Biol. Chem. 274:33426–33432.
Kirkwood, T. B. and Kowald, A. 1997. Network theory of aging. Exp. Gerontol. 32:395–399.
Sohal, R. S. 1997. Role of mitochondria and oxidative stress in the aging process. Pages 91–107, in Beal, M. F., Howell, N., Bodis-Wollner, I. (eds.), Mitochondria and Free Radicals in Neurodegenerative diseases, Wiley-Liss, New York.
Stadtman, E. R. 1992. Protein oxidation and aging. Science 257:1220–1224.
Stadtman, E. R. and Levine, R. L. 2000. Protein oxidation. Ann. NY Acad. Sci. 899:191–208.
Dyrks, T., Dyrks, E., Masters, C. L., and Beyreuther, K. 1993. Amyloidogenicity of rodent and human beta A4 sequences. FEBS Lett. 324, 231–236.
Smith, C. D., Carney, J. M., Tatsumo, T., Stadtman, E. R., Floyd, R. A., and Markesbery, W. R. 1992. Protein oxidation in aging brain. Ann. NY Acad. Sci. 663:110–119.
Smith, M. A., Perry, G., Richey, P. L., Sayre, L. M., Anderson, V. E., Beal, M. F., and Kowall, N. 1996. Oxidative damage in Alzheimer's. Nature 382:120–121.
Smith, M. A. and Perry, G. 1996. Alzheimer disease: Proteinprotein interaction and oxidative stress. Bol. Estud. Med. Biol. 44:5–10.
Mecocci, P., Beal, M. F., Cecchetti, R., Polidori, M. C., Cherubini, A., Chionne, F., Avellini, L., Romano, G., and Senin, U. 1997. Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain. Mol. Chem. Neuropathol. 31:53–64.
Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., and Beal, M. F. 1993. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann. Neurol. 34:609–616.
Paradies, G. and Ruggiero, F. M. 1990. Age-related changes in the activity of the pyruvate carrier and in the lipid composition in rat-heart mitochondria. Biochim. Biophys. Acta 1016:207–212.
Paradies, G., Petrosillo G., Gadaleta M. N., and Ruggiero, F. M. 1999. The effect of aging and acetyl-L-carnitine on the pyruvate transport and oxidation in rat heart mitochondria. FEBS Lett. 454:207–209.
Hagen, T. M., Yowe, D. L., Bartholomew, J. C., Wehr, C. M., Do, K. L., Park, J. Y., and Ames, B. N. 1997. Mitochondrial decay in hepatocytes from old rats: Membrane potential declines, heterogeneity and oxidants increase. Proc. Natl. Acad. Sci. USA 94:3064–3069.
Ozawa, T., Tanaka, M., Ikebe, S., Ohno, K., Kondo, T., and Mizuno, Y. 1990. Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. Biochem. Biophys. Res. Commun. 172:483–489.
Mecocci, P., MacGarvey, U., and Beal, M. F. 1994. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann. Neurol. 36:747–751.
Cottrell, D. A., Blakely, E. L., Johnson, M. A., Ince, P. G., Borthwick, G. M., and Turnbull, D. M. 2001. Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with age. Neurobiol. Aging 22:265–272.
Muller-Hocker, J. 1990. Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: An age-related alteration. J. Neurol. Sci. 100:14–21.
Cottrell, D. A. and Turnbull, D. M. 2000. Mitochondria and ageing. Curr. Opin. Clin. Nutr. Metab. Care 3:473–478.
Forster, M. J., Sohal, B. H., and Sohal, R. S. 2000. Reversible effects of long-term caloric restriction on protein oxidative damage. J. Gerontol. A. Biol. Sci. Med. Sci. 55:B522–529.
Feuers, R. J. 1998. The effects of dietary restriction on mitochondrial dysfunction in aging. Ann. NY Acad. Sci. 854:192–201.
Kristal, B. S. and Yu, B. P. 1998. Dietary restriction augments protection against induction of the mitochondrial permeability transition. Free Radic. Biol. Med. 24:1269–1277.
Yu, B. P. 1996. Aging and oxidative stress: Modulation by dietary restriction. Free Radic. Biol. Med. 21:651–668.
Hall, D. M., Oberley, T. D., Moseley, P. M., Buettner, G. R., Oberley, L. W., Weindruch, R., and Kregel, K. C. 2000. Caloric restriction improves thermotolerance and reduces hyperthermiainduced cellular damage in old rats. FASEB J. 14:78–86.
Lee, C. K., Klopp, R. G., Weindruch, R., and Prolla, T. A. 1999. Gene expression profile of aging and its retardation by caloric restriction. Science 285:1390–1393.
Cassarino, D. S. and Bennett, J. P. 1999. An evaluation of the role of mitochondria in neurodegenerative diseases: Mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. Brain Res. Brain Res. Rev. 29:1–25.
Beutner, G., Ruck, A., Riede, B., Welte, W., and Brdiczka, D. 1996. Complexes between kinases, mitochondrial porin and adenylate translocator in rat brain resemble the permeability transition pore. FEBS-Lett. 396:189–195.
Petronilli, V., Penzo, D., Scorrano, L., Bernardi, P., and Di Lisa, F. 2000. The mitochondrial permeability transition, release of cytochrome c and cell death. Correlation with the duration of pore openings in situ. J. Biol. Chem. 276:2571–2575.
Nicholls, D., Bernardi, P., Brand, M., Halestrap, A., Lemasters, J., and Reynolds, I. 2000. Apoptosis and the laws of thermodynamics. Nat. Cell. Biol. 2:E172–173.
Vieira, H. L. and Kroemer, G. 1999. Pathophysiology of mitochondrial cell death control. Cell. Mol. Life Sci. 56:971–976.
Greenamyre, J. T., MacKenzie, G., Peng, T. L., and Stephans, S. E. 1999. Mitochondrial dysfunction in Parkinson's disease. Biochem. Soc. Symp. 66:85–97.
Cassarino, D. S., Parks, J. K., Parker, W. D., and Bennett, J. P. 1999. The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism. Biochim. Biophys. Acta 1453:49–62.
Zoratti, M. and Szabo, I. 1995. The mitochondrial permeability transition. Biochim. Biophys. Acta 1241:139–176.
Kristal, B. S. and Dubinsky, J. M. 1997. Mitochondrial permeability transition in the central nervous system: Induction by calcium cycling-dependent and-independent pathways. J. Neurochem. 69:524–538.
Zamzami, N., Hirsch, T., Dallaporta, B., Petit, P. X., and Kroemer, G. 1997. Mitochondrial implication in accidental and programmed cell death: Apoptosis and necrosis. J. Bioenerg. Biomembr. 29:185–193.
Kannan, K. and Jain, S. K. 2000. Oxidative stress and apoptosis. Pathophysiology 7:153–163.
Storz, G. and Tartaglia, L. A. 1992. OxyR: A regulator of antioxidant genes. J. Nutr. 122:627–639.
Mattson, M., Culmsee, C., Zaifang, Yu., and Camandola, S. 2000. Roles of nuclear factor kB in neuronal survival and plasticity. J. Neurochem. 74:443–456.
Taylor, B. S., de Vera, M. E., Ganster, R. W., Wang, Q., Shapiro, R. A., Morris, S. M., Billiar, T. R., and Geller, D. A. 1998. Multiple NFkB enhancer elements regulate cytokine induction of the human inducible nitric oxide synthase gene. J. Biol. Chem. 273:15148–15156.
Mirza, A., Liu, S. L., Frizell, E., Zhu, J., Maddukuri, S., Martinez, J., Davies, P., Schwarting, R., Norton, P., and Zern, M. A. 1997. A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-kappaB. Am. J. Physiol. 272:281–288.
Zong, W. X., Edelstein, L. C., Chen, C., Bash, J., and Gelinas, C. 1999. The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalphainduced apoptosis. Genes Dev. 13:382–387.
Mattson, M. P., Goodman, Y., Luo, H., Fu, W., and Furukawa, K. 1997. Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: Evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. J. Neurosci. Res. 49:681–697.
Walton, M., Connor, B., Lawlor, P., Young, D., Sirimanne, E., Gluckman, P., Cole, G., and Dragunow, M. 1999. Neuronal death and survival in two models of hypoxic-ischemic brain damage. Brain Res. Brain Res. Rev. 29:137–168.
Matsuoka, K., Kitamura, Y., Okazaki, M., Terai, K., and Taniguchi, T. 1999. Kainic acid-induced activation of nuclear factor-kB in rat hippocampus. Exp. Brain Res. 124:215–222.
Yang, R., Mu, X., and Hayes, R. L. 1995. Increased cortical nuclear factor-kB DNA binding activity after traumatic brain injury in rats. Neurosci. Lett. 197:101–104.
Kaltschmidt, B., Uherek, M., Volk, B., Baeuerle, P. A., and Kaltschmidt, C. 1997. Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease. Proc. Natl. Acad. Sci. USA 94:2642–2647.
Migheli, A., Piva, R., Atzori, C., Troost, D., and Schiffer, D. 1997. c-Jun, JNK/SAPK kinases and transcription factor NFkappa B are selectively activated in astrocytes, but not motor neurons, in amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 56:1314–1322.
Bruce-Keller, A. J., Geddes, J. W., Knapp, P. E., McFall, R. W., Keller, J. N., Holtsberg, F. W., Parthasarathy, S., Steiner, S. M., and Mattson, M. P. 1999. Anti-death properties of TNF against metabolic poisoning: Mitochondrial stabilization by MnSOD. J. Neuroimmunol. 93:53–71.
Wang, C. Y., Mayo, M. W., Korneluk, R. G., Goeddel, D. V., and Baldwin, A. S. 1998. NF-kappaB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 28:1680–1683.
Qin, Z. H., Wang, Y., Nakai, M., and Chase, T. N. 1998. Nuclear factor-kappa B contributes to excitotoxin-induced apoptosis in rat striatum. Mol. Pharmacol. 53:33–42.
Kasibhatla, S., Brunner, T., Genestier, L., Echeverri, F., Mahboubi, A., and Green, D. R. 1998. DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1. Mol. Cell 4:543–551.
Sherman, M. Y. and Goldberg, A. L. 2001. Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative diseases. Neuron 29:15–32.
Mattson, M. P. 2000. Neuroprotective signaling and the aging brain: Take away my food and let me run. Brain Res. 2000 886:47–53.
Calabrese, V., Renis, M., Calderone, A., Russo, A., Reale, S., Barcellona, M. L., and Rizza, V. 1998. Stress proteins and SH-groups in oxidant-induced cell injury after chronic ethanol administration in rat. Free Rad. Biol. Med. 24:1159–1167.
Susuki, T., Mitake, S., and Murata, S. 1999. Presence of upstream and down-stream components of mitogen-activated protein kinase (MAPK) pathway in the PSD fraction of the rat forebrain. Brain Res. 840:36–44.
Ndubuisi M. I., Guo, G. G., Fried, V. A., Etlinger, J. D., and Sehgal, P. B. 1999. Cellular physiology of STAT 3: Where is the cytoplasmic monomer? J. Biol. Chem. 274:25499–25509.
Dell'Albani, P., Kahn, M. A., Cole, R., Condorelli, D. F., Giuffrida-Stella, A. M., and de Vellis, J. 1998. Oligodendroglial survival factors, PDGF-AA and CNTF, activate similar JAK/STAT signaling pathways. J. Neurosci. Res. 54:191–205.
Song, I., Kamboj, S., Xia, J., Dong, H., Liao, D., and Huganir, R. L. 1998. Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21:393–400.
Ohtsuka, K. and Suzuki, T. 2000. Roles of molecular chaperones in the nervous system. Brain Res. Bull. 53:141–146.
Kobayashi, Y., Kume, A., Li, M., Doyu, M., Hata, M., Ohtsuka, K., and Sobue, G. 2000. Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract. J. Biol. Chem. 275:8772–8778.
Yenay, M. A., Giffard, R., Sapolsky, R. M., and Steinberg, G. K. 1999. The neuroprotective potential of heat shock protein (HSP70). Mol. Med. Tod. 51:525–531.
Takeda, A., Perry, G., Abraham, N. G., Dwyer, B. E., Kutty, R. K., Laitinen, J. T., Petersen, R. B., and Smith, M. A. 2000. Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau. J. Biol. Chem. 275:5395–5399.
Yenari, M. A., Fink, S. L., Sun, G. H., Chang, L. K., Patel, M. K., Kunis, D. M., Onley, D., Ho, D. Y., Sapolsky, R. M., and Steinberg, G. K. 1998. Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy. Ann. Neurol. 44:584–591.
Hata, R., Gass, P., Mies, G., Wiessner, C., and Hossmann, K. A. 1998. Attenuated c-fos mRNA induction after middle cerebral artery occlusion in CREB knockout mice does not modulate focal ischemic injury. J. Cereb. Blood Flow Metab. 18:1325–1335.
Nishimura, R. N. and Dwyer, B. E. 1995. Pharmacological induction of heat shock protein 68 synthesis in cultured rat astrocytes. J. Biol. Chem. 270:29967–29970.
Deckel, A. W. 2001. Nitric oxide and nitric oxide synthase in Huntington's disease. J. Neurosci. Res. 64:99–107.
Santoro, M. G. 2000. Heat shock and the control of the stress response. Biochem. Pharmacol. 59:55–63.
Baek, S. H., Kim, J. Y., Choi, J. H., Park, E. M., Han, M. Y., Kim, C. H., Ahn, Y. S., and Park, Y. M. 2000. Reduced glutathione oxidation ratio and 8-OHdG accumulation by mild ischemic pretreatment. Brain Res. 856:28–36.
Han, J., Cheng, F., Yang, Z., and Dryhurst G. 1999. Inhibitors of mitochondrial respiration, iron (II) and hydroxyl radical evoke release and extracellular hydrolysis of glutathione in rat striatum and substantia nigra: Potential implications to Parkinson's disease. J. Neurochem. 73:1683–1695.
Partridge, R. S., Monroe, S. M., Parks, J. K., Johnson, K., Parker, W. D., Eatn, G. R., and Eaton, S. S. 1994. Spin trapping of azidyl and hydroxyl radicals in azide-inhibited submitochondrial particles. Arch. Biochem. Biophys. 310:210–217.
Smith, T. S. and Bennet, J. P. 1997. Mitochondrial toxins in models of neurodegenerative diseases. I: In vivo brain hydroxyl radical production during systemic MPTP treatment or following microdialysis infusion of methylpyridinium or azide ions. Brain Res. 765:183–188.
Bennett, M. C., Diamond, D. M., Stryker, S. L., Parks, J. K., and Parker, W. D. 1992. Cytochrome oxidase inhibition: A novel animal model of Alzheimer's disease. J. Geriatr. Psychiatry Neurol. 5:93–101.
Parks, J. K., Smith, T. S., Trimmer, P. A., Bennett, J. P. Jr., and Parker, W. D. Jr. 2001. Neurotoxic Abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J. Neurochem. 76:1050–1056.
Canevari, L., Clark, J. B., and Bates, T. E. 1999. beta-Amyloid fragment 25–35 selectively decreases complex IV activity in isolated mitochondria. FEBS Lett. 457:131–134.
Copani, A., Condorelli, F., Caruso, A., Vancheri, C., Sala, A., Giuffrida Stella, A. M., Canonico, P. L., Nicoletti, F., and Sortino, M. A. 1999. Mitotic signaling by beta-amyloid causes neuronal death. FASEB J. 13:2225–2234.
Christen, Y. 2000. Oxidative stress and Alzheimer disease. Am. J. Clin. Nutr. 71:621S–629S.
Munch, G., Schinzel, R., Loske, C., Wong, A., Durany, N., Li, J. J., Vlassara, H., Smith, M. A., Perry, G., and Riederer, P. 1998. Alzheimer's disease. Synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J. Neural Transm. 105:439–461.
Sayre, L. M., Perry, G., Harris, P. L., Liu, Y., Schubert, K. A., and Smith, M. A. 2000. 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.
Bartzokis, G., Sultzer, D., Cummings, J., Holt, L. E., Hance, D. B., Henderson, V. W., and Mintz, J. 2000. In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging. Arch. Gen. Psychiatry 57:47–53.
El Khoury, J., Hickman, S. E., Thomas, C. A., Loike, J. D., and Silverstein, S. C. 1998. Microglia, scavenger receptors, and the pathogenesis of Alzheimer's disease. Neurobiol. Aging 19:S81–84.
Lovell, M. A., Ehmann, W. D., Mattson, M. P., and Markesbery, W. R. 1997. Elevated 4-hydroxynonenal in ventricular fluid in Alzheimer's disease. Neurobiol. Aging 18:457–461.
Smith, M. A., Richey Harris, P. L. Sayre, L. M., Beckman, J. S., and Perry, G. 1997. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J. Neurosci. 17:2653–2657.
Schapira, A. H. V. 1999. Mitochondral involvement in Parkinson's disease, Huntington,s disease, hereditary spastic paraplegia and Friedreic's ataxia. Biochim. Biophys. Acta 1410:159–170.
Ilic, T. V., Jovanovic, M., Jovicic, A., and Tomovic, M. 1999. Oxidative stress indicators are elevated in de novo Parkinson's disease patients. Funct. Neurol. 14:141–147.
Dexter, D. T., Holley, A. E., Flitter, W. D., Slater, T. F., Wells, F. R., Daniel, S. E., Lees, A. J., Jenner, P., and Marsden, C. D. 1994. Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: An HPLC and ESR study. Mov. Disord. 9:92–97.
Dexter, D. T., Carayon, A., Javoy-Agid, F., Agid, Y., Wells, F. R., Daniel, S., Lees, A. J., Jenner, P., and Marsden C. D. 1991. Alterations in the levels of iron ferritin and other trace metals in Parkinson's diseases affecting the basal ganglia. Brain 114:1953–1975.
Li, H. and Dryhurst, G. 1997. Irreversible inhibition of mitochondrial complex I by 2-aminoethyl-3,4-dyhydro-5-hydroxy-2-benzothiazine-3-carboxylic acid (DHBT): A putative nigral endotoxin of relevance to Parkinson's disease. J. Neurochem. 69:1530–1541.
Spencer, J., Jenner, A., Aruoma, O., Evans, P., Jenner, P., Lees, A., Marsden, D., and Halliwell, B. 1994. Intense oxidative DNA damage promoted by L-DOPA and its metabolites. Implication for neurodegenerative diseases. FEBS Lett. 353:246–250.
Perry, T. L., Godin, D. V., and Hansen, S. 1982. Parkinson's disease: A disorder due to nigral glutathione deficiency? Neurosci. Lett. 33:305–310.
Sian, J., Dexter, D. T., and Lees, A. J. 1994. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting the basal ganglia. Ann. Neurol. 36:348–355.
Hunot, S., Brugg, B., Richard, D., Michel, P. P., Muriel, M. P., Ruberg, M., Faucheux, B. A., Agid, Y., and Hirsch, E. C. 1997. Nuclear Translocation of NF-kB is increased in dopaminergic neurons of patients with Parkinson's disease. Proc. Natl. Acad. Sci. USA 94:7531–7536.
France-Lanord, V., Brugg, B., Michel, P. P., Agid, Y., and Ruberg, M. 1997. Mitochondrial free radical signal in ceramidedependent apoptosis: A putative mechanism for neuronal death in Parkinson's disease. J. Neurochem. 69:1612–1621.
Jellinger, K. A. 2000. Cell death mechanisms in Parkinson's disease. J. Neural. Transm. 107:1–29.
Browne, S. E. 1997. Mitochondrial dysfunction and oxidative damage in Huntington's disease. in: Flint Beal, M., Howell, N., Bodis-Wollner, I. (eds.), Mitochondria and Free Radicals in Neurodegenerative diseases, Wiley-Liss, New York.
Li, S. H., Lam, S., Cheng, A. L., and Li, X. J. 2000. Intranuclear huntingtin increases the expression of caspase-1 and induces apoptosis. Hum. Mol. Genet. 9:2859–2867.
Eldadah, B. A. and Faden, A. I. 2000. Caspase pathways, neuronal apoptosis, and CNS injury. J. Neurotrauma 17:811–829.
Andrews, T. C., Weeks, R. A., Turjanski, N., Gunn, R. N., Watkins, L. H., Sahakian, B., Hodges, J. R., Rosser, A. E., Wood, N. W., and Brooks, D. J. 1999. Huntington's disease progression. PET and clinical observations. Brain 122:2353–2363.
Nicoli, F., Vion-Dury, J., Maloteaux, J. M., Delwaide, C., Confort-Gouny, S., Sciaky, M., and Cozzone, P. J. 1993. CSF and serum metabolic profile of patients with Huntington's chorea: A study by high resolution proton NMR spectroscopy and HPLC. Neurosci. Lett. 154:47–51.
Ricklefs, R. E. 1998. Evolutionary theories of aging: Confirmation of a fundamental predicition, with implication for the genetic basis and evolution of life span. Am. Nat. 152:24–44.
Zwaan, B. J. 1999. The evolutionary genetics of ageing and longevity. Heredity 82:589–597.
Harman, D. A. 1956. A theory based on free radical and radiation chemistry. J. Gerontology 11:298–300.
Szilard, L. 1959. On the nature of the aging process. PNAS 45:35–45.
Kirkwood, T. B. 1977. Evolution of ageing. Nature 270:301–304.
Goto, M. 2000. Werner's syndrome: From clinics to genetics. Clin. Exp. Rheumatol. 18:760–766.
Rothschild, H. and Jazwinski, S. 1998. Human longevity determinant genes. J. La State Med. Soc. 150:272–274.
Jazwinski, S. M. 1996. Longevity, genes and aging. Science 273:54–59.
Verbeke, P., Clark, B. F., and Rattan, S. I. 2000. Modulating cellular aging in vitro: Hormetic effects of repeated mild heat stress on protein oxidation and glycation. Exp. Gerontol. 35:787–794.
Glade, M. J. 2001. Benefits from caloric restriction-is it hormesis? Nutrition 17:78–82.
Parsons, P. A. 2000. Caloric restriction, metabolic efficiency and hormesis. Hum. Exp. Toxicol. 19:345–347.
Lave, L. B. 2001. Hormesis: Implications for Public Policy Regarding Toxicants. Annu. Rev. Public Health 22:63–67.
Rattan, S. 1998. The nature of Gerontogenes and Vitagenes. Ann. NY Acad. Sci. 854:55–60.
Giuffrida Stella, A. M. 1991. Macromolecular changes in the aging brain. Pages 317–328, in: Timiras, P. S. et al., (eds.), Plasticity and Regeneration of the nervous system, Plenum Press, New York.
Giuffrida Stella, A. M. and Lajtha, A. 1987. Macromolecular turnover in brain during aging. Gerontology 33:136–148.
Lenaz, G. 1998. Role of mitochondria in oxidative stress and ageing. Biochim. Biophys. Acta 1336:53–67.
Nicoletti, V., Caruso, A., Tendi, E., Privitera, A., Console, A., Calabrese, V., Spadaro, F., Ravagna, A., Copani, A., and Giuffrida Stella, A. M. 1998. Effect of nitric oxide synthase induction on the expression of mitochondrial respiratory chain subunits in mixed cortical and astroglial cell cultures. Biochimie. 80:871–881.
Lechner, H., Agnoli, A., Benzi, G., Tucek, S., and Giuffrida Stella, A. M. 1987. Cerebral metabolism in Aging and neurological disorders. Gerontology, 33:120–270.
Nicoletti, V. G., Tendi, E. A., Console, A., Privitera, A., Villa, R. F., Ragusa, N., and Giuffrida-Stella, A. M. 1998. Regulation of cytochrome c oxidase and FoFl-ATPase subunits expression in rat brain during aging. Neurochem. Res. 23:55–61.
Acetyl-L-carnitine. 1999. Altern. Med. Rev. 4:438–441.
Calabrese, V. and Rizza, V. 1999. Formation of propionate after short-term ethanol treatment and its interaction with the carnitine pool in rat. Alcohol 19:169–176.
Boerrigter, M. E., Franceschi, C., Arrigoni-Martelli, E., Wei, J. Y., and Vijg, J. 1993. The effect of L-carnitine and acetyl-L-carnitine on the disappearance of DNA single-strand breaks in human peripheral blood lymphocytes. Carcinogenesis 14:2131–2136.
Calabrese V. and Rizza, V. 1999. Effects of L-carnitine on the formation of fatty acid ethyl esters in brain and peripheral organs after short-term ethanol administration in rat. Neurochem. Res. 24:79–84.
Calabrese, V., Scapagnini, G., Catalano, D., Dinotta, F., Bates, T. E., Calvani, M., and Giuffrida Stella, A. M. 2001. Effects of acetyl-l-carnitine on the formation of fatty acid ethyl esters in brain and peripheral organs after short-term ethanol administration in rat. Neurochemical Res. 26:167–174.
Pettegrew, J. W., Levine, J., and McClure, R. J. 2000. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: Relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol. Psychiatry 5:616–632.
Thal, L. J., Calvani, M., Amato, A., and Carta, A. 2000. A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. Neurology 55:805–810.
Scarpini, E., Sacilotto, G., Baron, P., Cusini, M., and Scarlato, G. 1997. Effect of acetyl-L-carnitine in the treatment of painful peripheral neuropathies in HIV+ patients. J. Peripher. Nerv. Syst. 2:250–252.
Paradies, G., Ruggiero, F. M., Petrosillo, G., Gadaleta, M. N., and Quagliariello, E. 1995. Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: The effect of acetyl-L-carnitine. Mech. Ageing Dev. 84:103–112.
Paradies, G., Ruggiero, F. M., Petrosillo, G., Gadaleta, M. N., and Quagliariello, E. 1994. Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria. FEBS Lett. 350:213–215.
Paradies, G., Ruggiero, F. M., Gadaleta, M. N., and Quagliariello, E. 1992. The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. Biochim. Biophys. Acta 1103:324–326.
Gorini, A., D'Angelo, A., and Villa, R. F. 1998. Energy metabolism of synaptosomal subpopulations from different neuronal systems of rat hippocampus: Effect of L-acetylcarnitine administration in vivo. Neurochem. Res. 23:1485–1491.
Calvani, M. and Arrigoni-Martelli, E. 1999. Attenuation by acetyl-L-carnitine of neurological damage and biochemical derangement following brain ischemia and reperfusion. Int. J. Tissue React. 21:1–6.
Hagen, T. M., Wehr, C. M., and Ames, B. N. 1998. Mitochondrial decay in aging. Reversal through supplementation of acetyl-L-carnitine and N-tert-butyl-alpha-phenyl-nitrone. Ann. NY Acad. Sci. 854:214–223.
Hagen, T. M., Ingersoll, R. T., Wehr, C. M., Lykkesfeldt, J., Vinarsky, V., Bartholomew, J. C., Song, M. H., and Ames, B. N. 1998. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc. Natl. Acad. Sci. USA 95:9562–9566.
Brooks, J. O., Yesavage, J. A., Carta, A., and Bravi, D. 1998. Acetyl-l-carnitine slows decline in younger patients with Alzheimer's disease: A reanalysis of a double-blind, placebocontrolled study using the trilinear approach. Int. Psychogeriatr. 10:193–203.
Pettegrew, J. W., Klunk, W. E., and Panchalingam, K. 1995. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging 16:1–4.
Fernandez, E., Pallini, R., Tamburrini, G., Lauretti, L., Tancredi, A., and La Marca, F. 1995. Effects of levo-acetylcarnitine on second motoneuron survival after axotomy. Neurol. Res. 5:373–376.
Foreman, P. J., Perez-Polo, J. R., Angelucci, L., Ramacci, M. T., and Taglialatela, G. 1995. Effects of acetyl-L-carnitine treatment and stress exposure on the nerve growth factor receptor (p75NGFR) mRNA level in the central nervous system of aged rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 19:117–133.
Taglialatela, G., Caprioli, A., Giuliani, A., and Ghirardi, O. 1996. Spatial memory and NGF levels in aged rats: Natural variability and effects of acetyl-L-carnitine treatment. Exp. Gerontol. 31:577–587.
Butterfield, D. A. 1999. On methionine and Alzheimer's amyloid b-peptide (1–42)-induced oxidative stress. Neurobiology of Aging 20:339–342.
Butterfield, D. A. and Stadtman, E. R. 1997. Protein oxidation processes in aging brain. Adv. Cell Aging Gerontol. 2:161–191.
Varadarajan, S., Yatin, S., Aksenova, M., and Butterfield, D. A. 2000. Alzheimer's Amyloid β-peptide-associated free radical oxidative stress and neurotoxicity. J. Struct. Biol. 130:184–208.
Butterfield, D. A., Koppal, T., Subramaniam, R., and Yatin, S. 1999. Vitamin E as an antioxidant/free radical scavenger against amyloid β-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: Insights into Alzheimer's disease. Rev. Neurosci. 10:141–149.
Koppal, T., Subramaniam, R., Drake, J., Prasad, R. P., Dhillon, H., and Butterfield, D. A. 1998. Vitamin E protects against Alzheimer's amyloid peptide (25–35)-induced changes in neocortical synaptosomal membrane lipid structure and composition. Brain Res. 786:270–273.
Yatin, S. M., Kink, C. D., and Butterfield, D. A. 1999. In-vitro and in-vivo oxidative stress associated with Alzheimer's amyloid β-peptide (1–42). Neurobiology of Aging 20:325–330.
Jen, L. S., Hart, A. J., Jen, A., Relvas, J. B., and Gentleman, S. M. 1998. Alzheimer's peptide kills cells of retina in vivo. Nature 392:140–141.
Gwebu, E. T., Williams, J., Mathis, D., Warden, J. A., Selassie, M., Richardson, S., and Gwebu, N. T. 1997. Cytotoxicity of β-amyloid peptide 25–35 on vascular smooth muscle cells and attenuation by vitamin E. In Vitro Cell Dev. Biol. Anim. 33:672–673.
Thomas, T., Thomas, G., McLendon, C., Sutton, T., and Mullan, M. 1996. β-amyloid-mediated vasoactivity and vascular endothelial damage. Nature 380:168–171.
Zaman, Z., Roche, S., Fielden, P., Niriella, D. C., and Cayley, A. C. 1992. Plasma concentrations of vitamin A and E and carotenoids in Alzheimer's disease. Age Ageing 21:91–94.
Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R. Schafer, K., Grundman, M., Woodbury, P., Growdon, J., Cotman, C. W., Pfeiffer, E., Schneider, L. S., and Thal, L. J. 1997. A controlled trial of selegiline, alphatocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's disease cooperative study, N. Engl. J. Med. 336:1216–1222.
Peyser, C. E., Folstein, M., Chase, G. A., Starkstein, S., Brandt, J., Cockrell, J. R., Bylsma, F., Coyle, J. T., McHugh, P. R., and Folstein, S. E. 1995. Trial of d-β-tocopherol in Huntington's disease. Amer. J. Psychiatry 152:1771–1775.
Reider, C. R. and Paulson, G. W. 1997. Lou Gehrig and amyotrophic lateral sclerosis. Is vitamin E to be revisited? Arch. Neurol. 54:527–528.
Papa, S. 1996. Mitochondrial oxidative phosphorylation changes in the life span. Molecular aspects and physiopathological implications. Biochim. Biophys. Acta 1276:87–105.
Papa, S. and Skulachev, V. P. 1997. Reactive oxygen species,mitochondria, apoptosis and aging. Mol. Cell. Biochem. 174:305–319.
Papa, S., Scacco, S., Sardanelli, A. M., Vergari, R., Papa, F., Budde, S., van den Heuvel, L., and Smeitink, J. 2001. Mutation in the NDUFS4 gene of complex I abolishes cAMP-dependent activation of the complex in a child with fatal neurological syndrome. FEBS Lett. 489:259–262.
Hurst, R. D., Azam, S., Hurst, A., and Clark, J. B. 2001. Nitric-oxide-induced inhibition of glyceraldehyde-3-phosphate dehydrogenase may mediate reduced endothelial cell monolayer integrity in an in vitro model blood-brain barrier. Brain. Res. 894:181–188.
Cullingford, T. E., Bhakoo, K. K., Peuchen, S., Dolphin, C. T., and Clark, J. B. 1999. Regulation of the ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in astrocytes and meningeal fibroblasts. Implications in normal brain development and seizure neuropathologies. Adv. Exp. Med. Biol. 466:241–251.
Fujihara, S. M. and Nadler, S. G. 1999. Intranuclear targeted delivery of functional NF-kappaB by 70 kDa heat shock protein. EMBO J. 18:411–419.
Lutz, T., Westermann, B., Neupert, W., and Herrmann, J. M. 2001. The Mitochondrial Proteins Ssq1 and Jac1 are Required for the Assembly of Iron Sulfur Clusters in Mitochondria. J. Mol. Biol. 307:815–825.
- Mitochondrial Involvement in Brain Function and Dysfunction: Relevance to Aging, Neurodegenerative Disorders and Longevity
Volume 26, Issue 6 , pp 739-764
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- Oxidative stress
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- caloric restriction
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- 1. Section of Biochemistry and Molecular Biology, Department of Chemistry, Faculty of Medicine, University of Catania, Catania
- 2. Department of Neurochemistry, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, U.K