Skip to main content
SpringerLink
Log in

Mitochondrial Disorders in Alzheimer’s Disease

  • REVIEW
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Alzheimer’s disease is the most common age-related neurodegenerative disease. Understanding of its etiology and pathogenesis is constantly expanding. Thus, the increasing attention of researchers is directed to the study of the role of mitochondrial disorders. In addition, in recent years, the concept of Alzheimer’s disease as a stress-induced disease has begun to form more and more actively. The stress-induced damage to the neuronal system can trigger a vicious circle of pathological processes, among which mitochondrial dysfunctions have a significant place, since mitochondria represent a substantial component in the anti-stress activity of the cell. The study of mitochondrial disorders in Alzheimer’s disease is relevant for at least two reasons: first, as important pathogenetic component in this disease; second, due to vital role of mitochondria in formation of the body resistance to various conditions, including stressful ones, throughout the life. This literature review analyzes the results of a number of recent studies assessing potential significance of the mitochondrial disorders in Alzheimer’s disease. The probable mechanisms of mitochondrial disorders associated with the development of this disease are considered: bioenergetic dysfunctions, changes in mitochondrial DNA (including assessment of the significance of its haplogroup features), disorders in the dynamics of these organelles, oxidative damage to calcium channels, damage to MAM complexes (membranes associated with mitochondria; mitochondria-associated membranes), disruptions of the mitochondrial quality control system, mitochondrial permeability, etc. The issues of the “primary” or “secondary” mitochondrial damage in Alzheimer’s disease are discussed. Potentials for the development of new methods for diagnosis and therapy of mitochondrial disorders in Alzheimer’s disease are considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

APP:

amyloid precursor protein

MAM:

mitochondria-associated membranes

References

  1. Hardy, J. A., and Higgins, G. A. (1992) Alzheimer’s disease: the amyloid cascade hypothesis, Science, 256, 184-185, https://doi.org/10.1126/science.1566067.

    Article  CAS  PubMed  Google Scholar 

  2. Area-Gomez, E., de Groof, A., Bonilla, E., Montesinos, J., Tanji, K., et al. (2018) A key role for MAM in mediating mitochondrial dysfunction in Alzheimer disease, Cell Death Dis., 9, 335, https://doi.org/10.1038/s41419-017-0215-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mravec, B., Horvathova, L., and Padova, A. (2018) Brain under stress and Alzheimer’s disease, Cell. Mol. Neurobiol., 38, 73-84, https://doi.org/10.1007/s10571-017-0521-1.

    Article  CAS  PubMed  Google Scholar 

  4. Armstrong, R. A. (2019) Risk factors for Alzheimer’s disease, Folia Neuropathol., 57, 87-105, https://doi.org/10.5114/fn.2019.85929.

    Article  Google Scholar 

  5. Hoeijmakers, L., Ruigrok, S. R., Amelianchik, A., Ivan, D., van Dam, A. M., et al. (2017) Early-life stress lastingly alters the neuroinflammatory response to amyloid pathology in an Alzheimer’s disease mouse model, Brain Behav. Immun., 63, 160-175, https://doi.org/10.1016/j.bbi.2016.12.023.

    Article  CAS  PubMed  Google Scholar 

  6. Piirainen, S., Youssef, A., Song, C., Kalueff, A. V., Landreth, G. E., et al. (2017) Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer’s disease: the emerging role of microglia? Neurosci. Biobehav. Rev., 77, 148-164, https://doi.org/10.1016/j.neubiorev.2017.01.046.

    Article  CAS  PubMed  Google Scholar 

  7. Lahiri, D. K., and Maloney, B. (2010) The “LEARn” (Latent Early-life Associated Regulation) model integrates environmental risk factors and the developmental basis of Alzheimer’s disease, and proposes remedial steps, Exp. Gerontol., 45, 291-296, https://doi.org/10.1016/j.exger.2010.01.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Moreira, P. I., Carvalho, C., Zhu, X., Smith, M. A., and Perry, G. (2010) Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology, Biochim. Biophys. Acta, 1802, 2-10, https://doi.org/10.1016/j.bbadis.2009.10.006.

    Article  CAS  PubMed  Google Scholar 

  9. Santos, R. X., Correia, S. C., Wang, X., Perry, G., Smith, M. A., et al. (2010) A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease, J. Alzheimers Dis., 20 Suppl. 2, 401-412, https://doi.org/10.3233/JAD-2010-100666.

    Article  CAS  Google Scholar 

  10. Su, B., Wang, X., Bonda, D., Perry, G., Smith, M., and Zhu, X. (2010) Abnormal mitochondrial dynamics – a novel therapeutic target for Alzheimer’s disease? Mol. Neurobiol., 41, 87-96, https://doi.org/10.1007/s12035-009-8095-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Coskun, P. E., Wyrembak, J., Schriner, S., Chen, H. W., Marciniack, C., et al. (2013) A mitochondrial etiology of Alzheimer’s and Parkinson’s disease, Biochim. Biophys. Acta, 1820, 553-564, https://doi.org/10.1016/j.bbagen.2011.08.008.

    Article  CAS  Google Scholar 

  12. Spuch, C., Ortolano, S., and Navarro, C. (2012) New insights in the amyloid-beta interaction with mitochondria, J. Aging Res., 2012, 324968, https://doi.org/10.1155/2012/324968.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Young-Collier, K. J., McArdle, M., and Bennett, J. P. (2012) The dying of the light: mitochondrial failure in Alzheimer’s disease, J. Alzheimers Dis., 28, 771-781, https://doi.org/10.3233/JAD-2011-111487.

    Article  CAS  PubMed  Google Scholar 

  14. Swerdlow, R. H., Burns, J. M., and Khan, S. M. (2014) The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives, Biochim. Biophys. Acta, 1842, 1219-1231, https://doi.org/10.1016/j.bbadis.2013.09.010.

    Article  CAS  PubMed  Google Scholar 

  15. Cabezas-Opazo, F. A., Vergara-Pulgar, K., Pérez, M. J., Jara, C., Osorio-Fuentealba, C., and Quintanilla, R. A. (2015) Mitochondrial dysfunction contributes to the pathogenesis of Alzheimer’s disease, Oxid. Med. Cell. Longev., 2015, 509654, https://doi.org/10.1155/2015/509654.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Demetrius, L. A., and Driver, J. A. (2015) Preventing Alzheimer’s disease by means of natural selection, J. R. Soc. Interface, 12, 20140919, https://doi.org/10.1098/rsif.2014.0919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cai, Q., and Tammineni, P. (2016) Alterations in mitochondrial quality control in Alzheimer’s disease, Front. Cell. Neurosci., 10, 24, https://doi.org/10.3389/fncel.2016.00024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sukhorukov, V. S., Voronkova, A. S., Litvinova, N. A., Baranich, T. I., and Illarioshkin, S. N. (2020) The role of mitochondrial DNA individuality in the pathogenesis of Parkinson’s disease, Russ. J. Genet., 56, 392-400.

    Article  Google Scholar 

  19. Lukyanova, L. D. (2019) Signaling mechanisms of hypoxia, Moscow: RAS, p. 215.

  20. Lanzillotta, C., Di Domenico, F., Perluigi, M., Butterfield, D. A. (2019) Targeting mitochondria in Alzheimer disease: rationale and perspectives, CNS Drugs, 33, 957-969, https://doi.org/10.1007/s40263-019-00658-8.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Picone, P., Nuzzo, D., Giacomazza, D., and Carlo, M. D. (2020) β-Amyloid peptide: the cell compartment multi-faceted interaction in Alzheimer’s disease, Neurotox. Res., 37, 250-263, https://doi.org/10.1007/s12640-019-00116-9.

    Article  CAS  PubMed  Google Scholar 

  22. Beal, M. F. (1996) Mitochondria, free radicals and neurodegeneration, Curr. Opin. Neurobiol., 6, 661-666, https://doi.org/10.1016/s0959-4388(96)80100-0.

    Article  CAS  PubMed  Google Scholar 

  23. Bubber, P., Haroutunian, V., Fisch, G., Blass, J. P., and Gibson, G. E. (2005) Mitochondrial abnormalities in Alzheimer brain: mechanistic implications, Ann. Neurol., 57, 695-703, https://doi.org/10.1002/ana.20474.

    Article  CAS  PubMed  Google Scholar 

  24. Wallace, D. C. (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine, Annu. Rev. Genet., 39, 359-407, https://doi.org/10.1146/annurev.genet.39.110304.095751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sims, N. R., Finegan, J. M., Blass, J. P., Bowen, D. M., and Neary, D. (1987) Mitochondrial function in brain tissue in primary degenerative dementia, Brain Res., 436, 30-38, https://doi.org/10.1016/0006-8993(87)91553-8.

    Article  CAS  PubMed  Google Scholar 

  26. Aksenov, M. Y., Tucker, H. M., Nair, P., Aksenova, M. V., Butterfield, D. A., et al. (1999) The expression of several mitochondrial and nuclear genes encoding the subunits of electron transport chain enzyme complexes, cytochrome c oxidase and NADH dehydrogenase, in different brain regions in Alzheimer’s disease, Neurochem. Res., 24, 767-774, https://doi.org/10.1023/A:1020783614031.

    Article  CAS  PubMed  Google Scholar 

  27. Parker, W. D. Jr., Filley, C. M., and Parks, J. K. (1990) Cytochrome oxidase deficiency in Alzheimer’s disease, Neurology, 40, 1302-1303, https://doi.org/10.1212/WNL.40.8.1302.

    Article  PubMed  Google Scholar 

  28. Parker, W. D. Jr., Parks, J., Filley, C. M., and Kleinschmidt-Demasters, B. K. (1994) Electron transport chain defects in Alzheimer’s disease brain, Neurology, 44, 1090-1096, https://doi.org/10.1212/WNL.44.6.1090.

    Article  PubMed  Google Scholar 

  29. Maurer, I., Zierz, S., and Möller, H. J. (2000) A selective defect of cytochrome c oxidase is present in brain of Alzheimer’s disease patients, Neurobiol. Aging, 21, 455-462, https://doi.org/10.1016/s0197-4580(00)00112-3.

    Article  CAS  PubMed  Google Scholar 

  30. Kish, S. J., Mastrogiacomo, F., Guttman, M., Furukawa, Y., Taanman, J. W., et al. (1999) Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer’s disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change? J. Neurochem., 72, 700-707, https://doi.org/10.1046/j.1471-4159.1999.0720700.x.

    Article  CAS  PubMed  Google Scholar 

  31. Ohta, S., and Ohsawa, I. (2006) Dysfunction of mitochondria and oxidative stress in the pathogenesis of Alzheimer’s disease: on defects in the cytochrome c oxidase complex and aldehyde detoxification, J. Alzheimers Dis., 9, 155-166, https://doi.org/10.3233/jad-2006-9208.

    Article  PubMed  Google Scholar 

  32. Wilkins, H. M., and Swerdlow, R. H. (2017) Amyloid precursor protein processing and bioenergetics, Brain Res. Bull., 133, 71-79, https://doi.org/10.1016/j.brainresbull.2016.08.009.

    Article  CAS  PubMed  Google Scholar 

  33. Gibson, G. E., Chen, H. L., Xu, H., Qiu, L., Xu, Z., et al. (2012) Deficits in the mitochondrial enzyme α-ketoglutarate dehydrogenase lead to Alzheimer’s disease-like calcium dysregulation, Neurobiol. Aging, 33, 1121.e13-24, https://doi.org/10.1016/j.neurobiolaging.2011.11.003.

    Article  CAS  Google Scholar 

  34. Manczak, M., Anekonda, T. S., Henson, E., Park, B. S., Quinn, J., and Reddy, P. H. (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, 1437-1449, https://doi.org/10.1093/hmg/ddl066.

    Article  CAS  PubMed  Google Scholar 

  35. Nunomura, A., Castellani, R. J., Zhu, X., Moreira, P. I., Perry, G., and Smith, M. A. (2006) Involvement of oxidative stress in Alzheimer’s disease, J. Neuropathol. Exp. Neurol., 65, 631-641, https://doi.org/10.1097/01.jnen.0000228136.58062.bf.

    Article  CAS  PubMed  Google Scholar 

  36. Riemer, J., and Kins, S. (2013) Axonal transport and mitochondrial dysfunction in Alzheimer’s disease, Neurodegener. Dis., 12, 111-124, https://doi.org/10.1159/000342020.

    Article  CAS  PubMed  Google Scholar 

  37. Bonda, D. J., Wang, X., Perry, G., Smith, M. A., and Zhu, X. (2010) Mitochondrial dynamics in Alzheimer’s disease: opportunities for future treatment strategies, Drugs Aging, 27, 181-192, https://doi.org/10.2165/11532140-000000000-00000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nakamura, T., Cieplak, P., Cho, D. H., Godzik, A., and Lipton, S. A. (2010) S-nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration, Mitochondrion, 10, 573-578, https://doi.org/10.1016/j.mito.2010.04.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Poirier, Y., Grimm, A., Schmitt, K., and Eckert, A. (2019) Link between the unfolded protein response and dysregulation of mitochondrial bioenergetics in Alzheimer’s disease, Cell. Mol. Life Sci., 76, 1419-1431, https://doi.org/10.1007/s00018-019-03009-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hu, H., Tan, C. C., Tan, L., and Yu, J. T. (2017) A mitocentric view of Alzheimer’s disease, Mol. Neurobiol., 54, 6046-6060, https://doi.org/10.1007/s12035-016-0117-7.

    Article  CAS  PubMed  Google Scholar 

  41. Györffy, B. A., Tóth, V., Török, G., Gulyássy, P., Kovács, R. Á., et al. (2020) Synaptic mitochondrial dysfunction and septin accumulation are linked to complement-mediated synapse loss in an Alzheimer’s disease animal model, Cell. Mol. Life Sci., https://doi.org/10.1007/s00018-020-03468-0.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sukhorukov, V. S. (2011) Individual peculiarities of tissue energy metabolism and their role in the development of childhood diseases, Ros. Vestn. Perinatol. Pediat., 56, 4-11.

    Google Scholar 

  43. Sukhorukov, V. S. (2011) Notes on mitochondrial pathology, Medpraktika-M, Moscow, p. 288.

  44. Sukhorukov, V. S., Voronkova, A. S., Litvinova, N. A., Baranich, T. I., and Kharlamov, D. A. (2017) Significance of mitochondrial individuality, Adaptation Biology and Medicine (Kawai, Y., Hargens, A. R., and Singal, P. K., eds.) Vol. 8 Current Trends, Narosa Publishing House Pvt. Ltd., New Dehli, India, p. 27-41.

  45. Skulachev, V. P. (2006) Bioenergetic aspects of apoptosis, necrosis and mitoptosis, Apoptosis, 11, 473-485, https://doi.org/10.1007/s10495-006-5881-9.

    Article  CAS  PubMed  Google Scholar 

  46. O’Mealey, G. B., Plafker, K. S., Berry, W. L., Janknecht, R., Chan, J. Y., and Plafker, S. M. (2017) A PGAM5-KEAP1-Nrf2 complex is required for stress-induced mitochondrial retrograde trafficking, J. Cell Sci., 130, 3467-3480, https://doi.org/10.1242/jcs.203216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Trougakos, I. P. (2019) Nrf2, stress and aging, Aging (Albany NY), 11, 5289-5291, https://doi.org/10.18632/aging.102143.

    Article  Google Scholar 

  48. Tsakiri, E. N., Gumeni, S., Iliaki, K. K., Benaki, D., Vougas, K., et al. (2019) Hyperactivation of Nrf2 increases stress tolerance at the cost of aging acceleration due to metabolic deregulation, Aging Cell, 18, e12845, https://doi.org/10.1111/acel.12845.

    Article  CAS  PubMed  Google Scholar 

  49. Sabouny, R., Fraunberger, E., Geoffrion, M., Ng, A. C., Baird, S. D., et al. (2017) The Keap1-Nrf2 stress response pathway promotes mitochondrial hyperfusion through degradation of the mitochondrial fission protein Drp1, Antioxid. Redox Signal., 27, 1447-1459, https://doi.org/10.1089/ars.2016.6855.

    Article  CAS  PubMed  Google Scholar 

  50. Santoro, A., Balbi, V., Balducci, E., Pirazzini, C., Rosini, F., et al. (2010) Evidence for sub-haplogroup h5 of mitochondrial DNA as a risk factor for late onset Alzheimer’s disease, PLoS One, 5, e12037, https://doi.org/10.1371/journal.pone.0012037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ridge, P. G., Koop, A., Maxwell, T. J., Bailey, M. H., Swerdlow, R. H., et al. (2013) Alzheimer’s disease neuroimaging initiative. Mitochondrial haplotypes associated with biomarkers for Alzheimer’s disease, PLoS One, 8, e74158, https://doi.org/10.1371/journal.pone.0074158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Krishnan, K. J., Ratnaike, T. E., De Gruyter, H. L., Jaros, E., and Turnbull, D. M. (2012) Mitochondrial DNA deletions cause the biochemical defect observed in Alzheimer’s disease, Neurobiol. Aging, 33, 2210-2214, https://doi.org/10.1016/j.neurobiolaging.2011.08.009.

    Article  CAS  PubMed  Google Scholar 

  53. Coskun, P. E., Beal, M. F., and Wallace, D. C. (2004) Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication, Proc. Natl Acad. Sci. USA, 101, 10726-10731, https://doi.org/10.1073/pnas.0403649101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Podlesniy, P., Figueiro-Silva, J., Llado, A., Antonell, A., Sanchez-Valle, R., et al. (2013) Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer’s disease, Ann. Neurol., 74, 655-668, https://doi.org/10.1002/ana.23955.

    Article  CAS  PubMed  Google Scholar 

  55. Lunnon, K., Keohane, A., Pidsley, R., Newhouse, S., Riddoch-Contreras, J., et al. (2017) Mitochondrial genes are altered in blood early in Alzheimer’s disease, Neurobiol. Aging, 53, 36-47, https://doi.org/10.1016/j.neurobiolaging.2016.12.029.

    Article  CAS  PubMed  Google Scholar 

  56. Mancuso, M., Calsolaro, V., Orsucci, D., Siciliano, G., and Murri, L. (2009) Is there a primary role of the mitochondrial genome in Alzheimer’s disease? J. Bioenerg. Biomembr., 41, 411-416, https://doi.org/10.1007/s10863-009-9239-1.

    Article  CAS  PubMed  Google Scholar 

  57. Karch, C. M., and Goate, A. M. (2015) Alzheimer’s disease risk genes and mechanisms of disease pathogenesis, Biol. Psychiatry, 77, 43-51, https://doi.org/10.1016/j.biopsych.2014.05.006.

    Article  CAS  PubMed  Google Scholar 

  58. Sukhorukov, V. S., Voronkova, A. S., and Litvinova, N. A. (2015) Clinical relevance of individual mitochondrial DNA characteristics, Russ. Bull. Perinatol. Pediatr., 60, 10-21.

    Google Scholar 

  59. Wallace, D. (2007) Why do we still have a maternally inherited mitochondrial DNA? Insights from evolutionary medicine, Annu. Rev. Biochem., 76, 781-821, https://doi.org/10.1146/annurev.biochem.76.081205.150955.

    Article  CAS  PubMed  Google Scholar 

  60. Bi, R., Zhang, W., Yu, D., Li, X., Wang, H. Z., et al. (2015) Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer’s disease in Han Chinese, Neurobiol. Aging, 36, 1604, https://doi.org/10.1016/j.neurobiolaging.2014.10.009.

    Article  CAS  PubMed  Google Scholar 

  61. Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. F., et al. (1993) Mitochondrial DNA variants observed in Alzheimer’s disease and Parkinson’s disease patients, Genomics, 17, 171-184, https://doi.org/10.1006/geno.1993.1299.

    Article  CAS  PubMed  Google Scholar 

  62. Bandelt, H., Kloss-Brandstatter, A., and Richards, M. (2014) The case for the continuing use of the revised Cambridge Reference Sequence (rCRS) and the standardization of notation in human mitochondrial DNA studies, J. Hum. Genet., 59, 66-77, https://doi.org/10.1038/jhg.2013.120.

    Article  CAS  PubMed  Google Scholar 

  63. Marom, S., Friger, M., and Mishmar, D. (2017) MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association, Sci. Rep., 7, 43449, https://doi.org/10.1038/srep43449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Swerdlow, R. H., Koppel, S., Weidling, I., Hayley, C., Ji, Y., and Wilkins, H. M. (2017) Mitochondria, cybrids, aging, and Alzheimer’s disease, Prog. Mol. Biol. Transl. Sci., 146, 259-302, https://doi.org/10.1016/bs.pmbts.2016.12.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Burté, F., Carelli, V., Chinnery, P. F., and Yu-Wai-Man, P. (2015) Disturbed mitochondrial dynamics and neurodegenerative disorders, Nat. Rev. Neurol., 11, 11-24, https://doi.org/10.1038/nrneurol.2014.228.

    Article  CAS  PubMed  Google Scholar 

  66. Cho, D. H., Nakamura, T., Fang, J., Cieplak, P., Godzik, A., et al. (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury, Science, 324, 102-105, https://doi.org/10.1126/science.1171091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Joshi, A. U., Saw, N. L., Shamloo, M., and Mochly-Rosen, D. (2018) Drp1/Fis1 interaction mediates mitochondrial dysfunction, bioenergetic failure and cognitive decline in Alzheimer’s disease, Oncotarget, 9, 6128-6143, https://doi.org/10.18632/oncotarget.23640.

    Article  PubMed  Google Scholar 

  68. More, J., Galusso, N., Veloso, P., Montecinos, L., Finkelstein, J. P., et al. (2018) N-acetylcysteine prevents the spatial memory deficits and the redox-dependent RyR2 decrease displayed by an Alzheimer’s disease rat model, Front. Aging Neurosci., 10, 399, https://doi.org/10.3389/fnagi.2018.00399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kirouac, L., Rajic, A. J., Cribbs, D. H., and Padmanabhan, J. (2017) Activation of ras-ERK signaling and GSK-3 by amyloid precursor protein and amyloid beta facilitates neurodegeneration in Alzheimer’s disease, eNeuro, 4, ENEURO.0149-16.2017, https://doi.org/10.1523/ENEURO.0149-16.2017.

    Article  Google Scholar 

  70. Giorgi, C., Missiroli, S., Patergnani, S., Duszynski, J., Wieckowski, M. R., and Pinton, P. (2015) Mitochondria-associated membranes: composition, molecular mechanisms, and physiopathological implications, Antioxid. Redox Signal., 22, 995-1019, https://doi.org/10.1089/ars.2014.6223.

    Article  CAS  PubMed  Google Scholar 

  71. Bononi, A., Missiroli, S., Poletti, F., Suski, J. M., Agnoletto, C., et al. (2012) Mitochondria-associated membranes (MAMs) as hotspot Ca2+ signaling units, Adv. Exp. Med. Biol., 740, 411-437, https://doi.org/10.1007/978-94-007-2888-2_17.

    Article  CAS  PubMed  Google Scholar 

  72. Völgyi, K., Badics, K., Sialana, F. J., Gulyássy, P., Udvari, E. B., et al. (2018) Early presymptomatic changes in the proteome of mitochondria-associated membrane in the APP/PS1 mouse model of Alzheimer’s disease, Mol. Neurobiol., 55, 7839-7857, https://doi.org/10.1007/s12035-018-0955-6.

    Article  CAS  PubMed  Google Scholar 

  73. Contino, S., Porporato, P. E., Bird, M., Marinangeli, C., Opsomer, R., et al. (2017) Presenilin 2-dependent maintenance of mitochondrial oxidative capacity and morphology, Front. Physiol., 8, 796, https://doi.org/10.3389/fphys.2017.00796.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Rodríguez-Arribas, M., Yakhine-Diop, S. M. S., Pedro, J. M. B., Gómez-Suaga, P., Gómez-Sánchez, R., et al. (2017) Mitochondria-associated membranes (MAMs): overview and its role in Parkinson’s disease, Mol. Neurobiol., 54, 6287-6303, https://doi.org/10.1007/s12035-016-0140-8.

    Article  CAS  PubMed  Google Scholar 

  75. Area-Gomez, E., and Schon, E. A. (2016) Mitochondria-associated ER membranes and Alzheimer’s disease, Curr. Opin. Genet. Dev., 38, 90-96, https://doi.org/10.1016/j.gde.2016.04.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Area-Gomez, E., Del Carmen Lara Castillo, M., Tambini, M. D., Guardia-Laguarta, C., de Groof, A. J., et al. (2012) Upregulated function of mitochondria-associated ERmmembranes in Alzheimer’s disease, EMBO J., 31, 4106-4123, https://doi.org/10.1038/emboj.2012.202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Rusiño, A. E., Cui, Z., Chen, M. H., and Vance, J. E. (1994) A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins, J. Biol. Chem., 269, 27494-27502.

    Article  Google Scholar 

  78. Martin, L. A., Kennedy, B. E., and Karten, B. (2016) Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function, J. Bioenerg. Biomembr, 48, 137-151, https://doi.org/10.1007/s10863-014-9592-6.

    Article  CAS  PubMed  Google Scholar 

  79. Hedskog, L., Pinho, C. M., Filadi, R., Ronnback, A., Hertwig, L., et al. (2013) Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer’s disease and related models, Proc. Natl. Acad. Sci. USA, 110, 7916-7921, https://doi.org/10.1073/pnas.1300677110.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Kristofikova, Z., Springer, T., Gedeonova, E., Hofmannova, A., Ricny, J., et al. (2020) Interactions of 17β-hydroxysteroid dehydrogenase type 10 and cyclophilin D in Alzheimer’s disease, Neurochem. Res., 45, 915-927, https://doi.org/10.1007/s11064-020-02970-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Esterhuizen, K., van der Westhuizen, F. H., and Louw, R. (2017) Metabolomics of mitochondrial disease, Mitochondrion, 35, 97-110, https://doi.org/10.1016/j.mito.2017.05.012.

    Article  CAS  PubMed  Google Scholar 

  82. Pfleger, J., He, M., and Abdellatif, M. (2015) Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival, Cell Death Dis., 6, e1835, https://doi.org/10.1038/cddis.2015.202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bell, S. M., Barnes, K., De Marco, M., Shaw, P. J., Ferraiuolo, L., et al. (2021) Mitochondrial dysfunction in Alzheimer’s disease: a biomarker of the future? Biomedicines, 9, 63, https://doi.org/10.3390/biomedicines9010063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Grivennikova, V. G., and Vinogradov, A. D. (2013) Generation of active oxygen species by mitochondris, Adv. Biol. Chem., 53, 245-296.

    Google Scholar 

  85. Oliver, D. M. A., and Reddy, P. H. (2019) Small molecules as therapeutic drugs for Alzheimer’s disease, Mol. Cell. Neurosci., 96, 47-62, https://doi.org/10.1016/j.mcn.2019.03.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Van Giau, V., An, S. S. A., and Hulme, J. P. (2018) Mitochondrial therapeutic interventions in Alzheimer’s disease, J. Neurol. Sci., 15, 62-70, https://doi.org/10.1016/j.jns.2018.09.033.

    Article  CAS  Google Scholar 

  87. Komaki, H., Faraji, N., Komaki, A., Shahidi, S., Etaee, F., et al. (2019) Investigation of protective effects of coenzyme Q10 on impaired synaptic plasticity in a male rat model of Alzheimer’s disease, Brain Res. Bull., 147, 14-21, https://doi.org/10.1016/j.brainresbull.2019.01.025.

    Article  CAS  PubMed  Google Scholar 

  88. Wang, H., Li, L., Jia, K., Wang, Q., Sui, S., et al. (2020) Idebenone protects mitochondrial function against amyloid beta toxicity in primary cultured cortical neurons, Neuroreport, 31, 1104-1110, https://doi.org/10.1097/WNR.0000000000001526.

    Article  CAS  PubMed  Google Scholar 

  89. Kapay, N. A., Isaev, N. K., Stelmashook, E. V., Popova, O. V., Zorov, D. B., et al. (2011) In vivo injected mitochondria-targeted plastoquinone antioxidant SkQR1 prevents β-amyloid-induced decay of long-term potentiation in rat hippocampal slices, Biochemistry (Moscow), 76, 1367-1370, https://doi.org/10.1134/S0006297911120108.

    Article  CAS  Google Scholar 

  90. Snow, W. M., Cadonic, C., Cortes-Perez, C., Adlimoghaddam, A., Roy Chowdhury, S. K., et al. (2020) Sex-specific effects of chronic creatine supplementation on hippocampal-mediated spatial cognition in the 3xTg mouse model of Alzheimer’s disease, Nutrients, 12, 3589, https://doi.org/10.3390/nu12113589.

    Article  CAS  PubMed Central  Google Scholar 

  91. Shinto, L., Quinn, J., Montine, T., Dodge, H. H., Woodward, W., et al. (2014) A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease, J. Alzheimer’s Dis., 38, 111-1120, https://doi.org/10.3233/JAD-130722.

    Article  CAS  Google Scholar 

  92. Auchter, A. M., Barrett, D. W., Monfils, M. H., and Gonzalez-Lima, F. (2020) Methylene blue preserves cytochrome oxidase activity and prevents neurodegeneration and memory impairment in rats with chronic cerebral hypoperfusion, Front. Cell Neurosci., 14, 130, https://doi.org/10.3389/fncel.2020.00130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chu, Q., Zhu, Y., Cao, T., Zhang, Y., Chang, Z., et al. (2020) Studies on the neuroprotection of osthole on glutamate-induced apoptotic cells and an Alzheimer’s disease mouse model via modulation oxidative stress, Appl. Biochem. Biotechnol., 190, 634-644, https://doi.org/10.1007/s12010-019-03101-2.

    Article  CAS  PubMed  Google Scholar 

  94. Chen, Q., Prior, M., Dargusch, R., Roberts, A., Riek, R., et al. (2011) A novel neurotrophic drug for cognitive enhancement and Alzheimer’s disease, PLoS One, 6, e27865, https://doi.org/10.1371/journal.pone.0027865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Hardie, D. G., Ross, F. A., and Hawley, S. A. (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis, Nat. Rev. Mol. Cell Biol., 13, 251-262, https://doi.org/10.1038/nrm3311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Goldberg, J., Currais, A., Prior, M., Fischer, W., Chiruta, C., et al. (2018) The mitochondrial ATP synthase is a shared drug target for aging and dementia, Aging Cell, 17, e12715, https://doi.org/10.1111/acel.12715.

    Article  CAS  PubMed Central  Google Scholar 

  97. Joshi, A. U., Minhas, P. S., Liddelow, S. A., Haileselassie, B., Andreasson, K. I., et al. (2019) Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration, Nat. Neurosci., 22, 1635-1648, https://doi.org/10.1038/s41593-019-0486-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Tsai, M. C., Lin, S. H., Hidayah, K., and Lin, C. I. (2019) Equol pretreatment protection of SH-SY5Y cells against Aβ (25-35)-induced cytotoxicity and cell-cycle reentry via sustaining estrogen receptor alpha expression, Nutrients, 11, 2356, https://doi.org/10.3390/nu11102356.

    Article  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Center of Neurology, 125367, Moscow, Russia

    Vladimir S. Sukhorukov, Natalia M. Mudzhiri, Anastasia S. Voronkova, Tatiana I. Baranich & Sergey N. Illarioshkin

  2. Pirogov Russian National Research Medical University (Pirogov Medical University), 117997, Moscow, Russia

    Tatiana I. Baranich & Valeria V. Glinkina

Authors
  1. Vladimir S. Sukhorukov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natalia M. Mudzhiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anastasia S. Voronkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tatiana I. Baranich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Valeria V. Glinkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sergey N. Illarioshkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Natalia M. Mudzhiri.

Ethics declarations

The authors declare no conflict of interest in financial or any other spheres. This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sukhorukov, V.S., Mudzhiri, N.M., Voronkova, A.S. et al. Mitochondrial Disorders in Alzheimer’s Disease. Biochemistry Moscow 86, 667–679 (2021). https://doi.org/10.1134/S0006297921060055

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297921060055

Keywords

Search

Navigation