Drug Target to Alleviate Mitochondrial Dysfunctions in Alzheimer’s Disease: Recent Advances and Therapeutic Implications


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Abstract

:Alzheimer's disease (AD) is a severe progressive neurodegenerative condition associated with neuronal damage and reduced cognitive function that primarily affects the aged worldwide. While there is increasing evidence suggesting that mitochondrial dysfunction is one of the most significant factors contributing to AD, its accurate pathobiology remains unclear. Mitochondrial bioenergetics and homeostasis are impaired and defected during AD pathogenesis. However, the potential of mutations in nuclear or mitochondrial DNA encoding mitochondrial constituents to cause mitochondrial dysfunction has been considered since it is one of the intracellular processes commonly compromised in early AD stages. Additionally, electron transport chain dysfunction and mitochondrial pathological protein interactions are related to mitochondrial dysfunction in AD. Many mitochondrial parameters decline during aging, causing an imbalance in reactive oxygen species (ROS) production, leading to oxidative stress in age-related AD. Moreover, neuroinflammation is another potential causative factor in AD-associated mitochondrial dysfunction. While several treatments targeting mitochondrial dysfunction have undergone preclinical studies, few have been successful in clinical trials. Therefore, this review discusses the molecular mechanisms and different therapeutic approaches for correcting mitochondrial dysfunction in AD, which have the potential to advance the future development of novel drug-based AD interventions.

About the authors

Md. Rahman

Department of Pathology, College of Korean Medicine, Kyung Hee University

Author for correspondence.
Email: info@benthamscience.net

MD. Rahman

Department of Pathology, College of Korean Medicine, Kyung Hee University

Email: info@benthamscience.net

Hyewhon Rhim

Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST)

Author for correspondence.
Email: info@benthamscience.net

Bonglee Kim

Department of Pathology, College of Korean Medicine, Kyung Hee University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Cenini, G.; Voos, W. Mitochondria as potential targets in alzheimer disease therapy: An update. Front Pharmacol., 2019, 10, ARTN 902. doi: 10.3389/fphar.2019.00902
  2. Carvalho, C.; Correia, S.C.; Cardoso, S.; Plácido, A.I.; Candeias, E.; Duarte, A.I.; Moreira, P.I. The role of mitochondrial disturbances in Alzheimer, Parkinson and Huntington diseases. Expert Rev. Neurother., 2015, 15(8), 867-884. doi: 10.1586/14737175.2015.1058160 PMID: 26092668
  3. Correia, S.C.; Santos, R.X.; Cardoso, S.; Carvalho, C.; Candeias, E.; Duarte, A.I.; Plácido, A.I.; Santos, M.S.; Moreira, P.I. Alzheimer disease as a vascular disorder: Where do mitochondria fit? Exp. Gerontol., 2012, 47(11), 878-886. doi: 10.1016/j.exger.2012.07.006 PMID: 22824543
  4. Bhatia, S.; Rawal, R.; Sharma, P.; Singh, T.; Singh, M.; Singh, V. Mitochondrial dysfunction in Alzheimer’s disease: Opportunities for drug development. Curr. Neuropharmacol., 2022, 20(4), 675-692. doi: 10.2174/1570159X19666210517114016 PMID: 33998995
  5. Ke, J.; Tian, Q.; Xu, Q.; Fu, Z.; Fu, Q. Mitochondrial dysfunction: A potential target for Alzheimer’s disease intervention and treatment. Drug Discov. Today, 2021, 26(8), 1991-2002. doi: 10.1016/j.drudis.2021.04.025 PMID: 33962036
  6. Zhang, Y.; Yang, H.; Wei, D.; Zhang, X.; Wang, J.; Wu, X.; Chang, J. Mitochondria‐targeted nanoparticles in treatment of neurodegenerative diseases. In: Exploration; Wiley Online Library, 2021; p. 20210115.
  7. Bai, R.; Guo, J.; Ye, X.Y.; Xie, Y.; Xie, T. Oxidative stress: The core pathogenesis and mechanism of Alzheimer’s disease. Ageing Res. Rev., 2022, 77, 101619. doi: 10.1016/j.arr.2022.101619 PMID: 35395415
  8. Gowda, P.; Reddy, P.H.; Kumar, S. Deregulated mitochondrial microRNAs in Alzheimer’s disease: Focus on synapse and mitochondria. Ageing Res. Rev., 2022, 73, 101529. doi: 10.1016/j.arr.2021.101529 PMID: 34813976
  9. Sun, Q.; Li, Y.; Shi, L.; Hussain, R.; Mehmood, K.; Tang, Z.; Zhang, H. Heavy metals induced mitochondrial dysfunction in animals: Molecular mechanism of toxicity. Toxicology, 2022, 469, 153136. doi: 10.1016/j.tox.2022.153136 PMID: 35202761
  10. Pelucchi, S.; Gardoni, F.; Di Luca, M.; Marcello, E. Synaptic dysfunction in early phases of Alzheimer’s disease. Handb. Clin. Neurol., 2022, 184, 417-438. doi: 10.1016/B978-0-12-819410-2.00022-9 PMID: 35034752
  11. Sorgdrager, F.J.H.; Vermeiren, Y.; Faassen, M.; Ley, C.; Nollen, E.A.A.; Kema, I.P.; De Deyn, P.P. Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease. J. Neurochem., 2019, 151(5), 656-668. doi: 10.1111/jnc.14843 PMID: 31376341
  12. Castro-Chavira, S.A.; Fernandez, T.; Nicolini, H.; Diaz-Cintra, S.; Prado-Alcala, R.A. Genetic markers in biological fluids for aging-related major neurocognitive disorder. Curr. Alzheimer Res., 2015, 12(3), 200-209. doi: 10.2174/1567205012666150302155138 PMID: 25731625
  13. Rahman, M.A.; Rhim, H. Therapeutic implication of autophagy in neurodegenerative diseases. BMB Rep., 2017, 50(7), 345-354. doi: 10.5483/BMBRep.2017.50.7.069 PMID: 28454606
  14. Moya-Alvarado, G.; Gershoni-Emek, N.; Perlson, E.; Bronfman, F.C. Neurodegeneration and Alzheimer’s disease (AD). What can proteomics tell us about the Alzheimer’s brain? Mol. Cell. Proteomics, 2016, 15(2), 409-425. doi: 10.1074/mcp.R115.053330 PMID: 26657538
  15. Rahman, M.A.; Rahman, M.S.; Uddin, M.J.; Mamum-Or-Rashid, A.N.M.; Pang, M.G.; Rhim, H. Emerging risk of environmental factors: Insight mechanisms of Alzheimer’s diseases. Environ. Sci. Pollut. Res. Int., 2020, 27(36), 44659-44672. doi: 10.1007/s11356-020-08243-z PMID: 32201908
  16. Rahman, M.A.; Rahman, M.S.; Rahman, M.H.; Rasheduzzaman, M.; Mamun-Or-Rashid, A.N.M.; Uddin, M.J.; Rahman, M.R.; Hwang, H.; Pang, M.G.; Rhim, H. Modulatory effects of autophagy on APP processing as a potential treatment target for Alzheimer's disease. Biomedicines, 2020, 9, 5. doi: 10.3390/biomedicines9010005
  17. Liang, S.Y.; Wang, Z.T.; Tan, L.; Yu, J.T. Tau toxicity in neurodegeneration. Mol. Neurobiol., 2022, 59(6), 3617-3634. doi: 10.1007/s12035-022-02809-3 PMID: 35359226
  18. González, A.; Singh, S.K.; Churruca, M.; Maccioni, R.B. Alzheimer’s disease and tau self-assembly: In the search of the missing link. Int. J. Mol. Sci., 2022, 23(8), 4192. doi: 10.3390/ijms23084192 PMID: 35457009
  19. Ye, H.; Han, Y.; Li, P.; Su, Z.; Huang, Y. The role of post-translational modifications on the structure and function of tau protein. J. Mol. Neurosci., 2022, 72(8), 1557-1571. doi: 10.1007/s12031-022-02002-0 PMID: 35325356
  20. Dhapola, R.; Sarma, P.; Medhi, B.; Prakash, A.; Reddy, D.H. Recent advances in molecular pathways and therapeutic implications targeting mitochondrial dysfunction for Alzheimer’s disease. Mol. Neurobiol., 2022, 59(2022), 535-555. doi: 10.1007/s12035-021-02612-6
  21. Zhao, Y.; Jia, M.; Chen, W.; Liu, Z. The neuroprotective effects of intermittent fasting on brain aging and neurodegenerative diseases via regulating mitochondrial function. Free Radic. Biol. Med., 2022, 182, 206-218. doi: 10.1016/j.freeradbiomed.2022.02.021
  22. Du, F.; Yu, Q.; Kanaan, N.M.; Yan, S.S. Mitochondrial oxidative stress contributes to the pathological aggregation and accumulation of tau oligomers in Alzheimer’s disease. Hum. Mol. Genet., 2022, 31(15), 2498-2507. doi: 10.1093/hmg/ddab363 PMID: 35165721
  23. Gong, W.; Xu, J.; Wang, Y.; Min, Q.; Chen, X.; Zhang, W.; Chen, J.; Zhan, Q. Nuclear genome-derived circular RNA circPUM1 localizes in mitochondria and regulates oxidative phosphorylation in esophageal squamous cell carcinoma. Signal. Transduct. Target. Ther., 2022, 7(1), 40. doi: 10.1038/s41392-021-00865-0 PMID: 35153295
  24. Zinovkin, R.A.; Zamyatnin, A.A., Jr Mitochondria-targeted drugs. Curr. Mol. Pharmacol., 2019, 12(3), 202-214. doi: 10.2174/1874467212666181127151059 PMID: 30479224
  25. Almendro-Vedia, V.; Natale, P.; Valdivieso González, D.; Lillo, M.P.; Aragones, J.L.; López-Montero, I. How rotating ATP synthases can modulate membrane structure. Arch. Biochem. Biophys., 2021, 708, 108939. doi: 10.1016/j.abb.2021.108939 PMID: 34052190
  26. Garbincius, J.F.; Elrod, J.W. Mitochondrial calcium exchange in physiology and disease. Physiol. Rev., 2022, 102(2), 893-992. doi: 10.1152/physrev.00041.2020 PMID: 34698550
  27. Schapira, A.H.V. Mitochondrial disease. Lancet, 2006, 368(9529), 70-82. doi: 10.1016/S0140-6736(06)68970-8 PMID: 16815381
  28. Cheung, G.; Bataveljic, D.; Visser, J.; Kumar, N.; Moulard, J.; Dallérac, G.; Mozheiko, D.; Rollenhagen, A.; Ezan, P.; Mongin, C.; Chever, O.; Bemelmans, A.P.; Lübke, J.; Leray, I.; Rouach, N. Physiological synaptic activity and recognition memory require astroglial glutamine. Nat. Commun., 2022, 13(1), 753. doi: 10.1038/s41467-022-28331-7 PMID: 35136061
  29. Birsoy, K.; Wang, T.; Chen, W.W.; Freinkman, E.; Abu-Remaileh, M.; Sabatini, D.M. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell, 2015, 162(3), 540-551. doi: 10.1016/j.cell.2015.07.016 PMID: 26232224
  30. Tabassum, N.; Kheya, I.S.; Asaduzzaman, S.; Maniha, S.; Fayz, A.H.; Zakaria, A.; Noor, R. A review on the possible leakage of electrons through the electron transport chain within mitochondria. Life Sci., 2020, 6, 105-113.
  31. Mani, S.; Swargiary, G.; Tyagi, S.; Singh, M.; Jha, N.K.; Singh, K.K. Nanotherapeutic approaches to target mitochondria in cancer. Life Sci., 2021, 281, 119773. doi: 10.1016/j.lfs.2021.119773 PMID: 34192595
  32. Horie, M.; Tabei, Y. Role of oxidative stress in nanoparticles toxicity. Free Radic. Res., 2021, 55(4), 331-342. doi: 10.1080/10715762.2020.1859108 PMID: 33336617
  33. Aruoma, O. Alzheimer’s disease and Parkinson’s disease: A nutritional toxicology perspective of the impact of oxidative Str.
  34. Rahman, M.A.; Rahman, M.D.H.; Biswas, P.; Hossain, M.S.; Islam, R.; Hannan, M.A.; Uddin, M.J.; Rhim, H. Potential therapeutic role of phytochemicals to mitigate mitochondrial dysfunctions in Alzheimer’s disease. Antioxidants, 2020, 10(1), 23. doi: 10.3390/antiox10010023 PMID: 33379372
  35. Sharma, C.; Kim, S.; Nam, Y.; Jung, U.J.; Kim, S.R. Mitochondrial dysfunction as a driver of cognitive impairment in Alzheimer’s disease. Int. J. Mol. Sci., 2021, 22(9), 4850. doi: 10.3390/ijms22094850 PMID: 34063708
  36. Brillo, V.; Chieregato, L.; Leanza, L.; Muccioli, S.; Costa, R. Mitochondrial dynamics, ROS, and cell signaling: A blended overview. Life (Basel), 2021, 11(4), 332. doi: 10.3390/life11040332 PMID: 33920160
  37. Rahman, M.; Hannan, M.; Uddin, M.; Rahman, M.; Rashid, M.; Kim, B. Exposure to environmental arsenic and emerging risk of Alzheimer’s disease: Perspective mechanisms, management strategy, and future directions. Toxics, 2021, 9(8), 188. doi: 10.3390/toxics9080188 PMID: 34437506
  38. Rahman, M.A.; Rahman, M.H.; Mamun-Or-Rashid, A.N.M.; Hwang, H.; Chung, S.; Kim, B.; Rhim, H. Autophagy modulation in aggresome formation: Emerging implications and treatments of Alzheimer’s disease. Biomedicines., 2022, 10(5), 1027. doi: 10.3390/biomedicines10051027 PMID: 35625764
  39. Bera, A.; Lavanya, G.; Reshmi, R.; Dev, K.; Kumar, R. Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer’s disease. Eur. J. Neurosci., 2022, 56, 5516-5531.
  40. Mondala, T.; Samantaa, S.; Kumara, A.; Govindarajua, T. Multifunctional inhibitors of multifaceted Aβ toxicity of Alzheimer's disease. In: Alzheimer’s Disease: Recent Findings in Pathophysiology, Diagnostic and Therapeutic Modalities; Royal Society of Chemistry, 2022.
  41. Taliyan, R.; Kakoty, V.; Sarathlal, K.C.; Kharavtekar, S.S.; Karennanavar, C.R.; Choudhary, Y.K.; Singhvi, G.; Riadi, Y.; Dubey, S.K.; Kesharwani, P. Nanocarrier mediated drug delivery as an impeccable therapeutic approach against Alzheimer’s disease. J. Control. Release, 2022, 343, 528-550. doi: 10.1016/j.jconrel.2022.01.044 PMID: 35114208
  42. Bomba-Warczak, E.; Savas, J.N. Long-lived mitochondrial proteins and why they exist. Trends Cell Biol., 2022, 32(8), 646-654. doi: 10.1016/j.tcb.2022.02.001 PMID: 35221146
  43. Xie, L.; Shi, F.; Tan, Z.; Li, Y.; Bode, A.M.; Cao, Y. Mitochondrial network structure homeostasis and cell death. Cancer Sci., 2018, 109(12), 3686-3694. doi: 10.1111/cas.13830 PMID: 30312515
  44. Wang, X.; Su, B.; Lee, H.; Li, X.; Perry, G.; Smith, M.A.; Zhu, X. Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J. Neurosci., 2009, 29(28), 9090-9103. doi: 10.1523/JNEUROSCI.1357-09.2009 PMID: 19605646
  45. Boguszewska, K.; Szewczuk, M.; Kaźmierczak-Barańska, J.; Karwowski, B.T. The similarities between human mitochondria and bacteria in the context of structure, genome, and base excision repair system. Molecules, 2020, 25(12), 2857. doi: 10.3390/molecules25122857 PMID: 32575813
  46. Kim, D.K.; Mook-Jung, I. The role of cell type-specific mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease. BMB Rep., 2019, 52(12), 679-688. doi: 10.5483/BMBRep.2019.52.12.282 PMID: 31722781
  47. Liu, X.; Zhang, Y.; Ni, M.; Cao, H.; Signer, R.A.J.; Li, D.; Li, M.; Gu, Z.; Hu, Z.; Dickerson, K.E.; Weinberg, S.E.; Chandel, N.S.; DeBerardinis, R.J.; Zhou, F.; Shao, Z.; Xu, J. Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation. Nat. Cell Biol., 2017, 19(6), 626-638. doi: 10.1038/ncb3527 PMID: 28504707
  48. Ding, X.W.; Robinson, M.; Li, R.; Aldhowayan, H.; Geetha, T.; Babu, J.R. Mitochondrial dysfunction and beneficial effects of mitochondria-targeted small peptide SS-31 in diabetes mellitus and Alzheimer’s disease. Pharmacol. Res., 2021, 171, 105783. doi: 10.1016/j.phrs.2021.105783 PMID: 34302976
  49. Bilbao-Malavé, V.; González-Zamora, J.; de la Puente, M.; Recalde, S.; Fernandez-Robredo, P.; Hernandez, M.; Layana, A.G.; Saenz de Viteri, M. Mitochondrial dysfunction and endoplasmic reticulum stress in age related macular degeneration, role in pathophysiology, and possible new therapeutic strategies. Antioxidants, 2021, 10(8), 1170. doi: 10.3390/antiox10081170 PMID: 34439418
  50. Machrina, Y.; Lindarto, D.; Pane, Y.S.; Harahap, N.S. The pattern of peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene expression in type-2 diabetes mellitus rat model liver: Focus on exercise. Open Access Maced. J. Med. Sci., 2021, 9(T3), 124-128. doi: 10.3889/oamjms.2021.6362
  51. Wang, C.F.; Song, C.Y.; Wang, X.; Huang, L.Y.; Ding, M.; Yang, H.; Wang, P.; Xu, L.L.; Xie, Z.H.; Bi, J.Z. Protective effects of melatonin on mitochondrial biogenesis and mitochondrial structure and function in the HEK293-APPswe cell model of Alzheimer’s disease. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(8), 3542-3550. PMID: 31081111
  52. Singulani, M.P.; Pereira, C.P.M.; Ferreira, A.F.F.; Garcia, P.C.; Ferrari, G.D.; Alberici, L.C.; Britto, L.R. Impairment of PGC-1α-mediated mitochondrial biogenesis precedes mitochondrial dysfunction and Alzheimer’s pathology in the 3xTg mouse model of Alzheimer’s disease. Exp. Gerontol., 2020, 133, 110882. doi: 10.1016/j.exger.2020.110882 PMID: 32084533
  53. Tiwari, S.; Dewry, R.K.; Srivastava, R.; Nath, S.; Mohanty, T.K. Targeted antioxidant delivery modulates mitochondrial functions, ameliorates oxidative stress and preserve sperm quality during cryopreservation. Theriogenology, 2022, 179, 22-31. doi: 10.1016/j.theriogenology.2021.11.013 PMID: 34823058
  54. Durairajanayagam, D.; Singh, D.; Agarwal, A.; Henkel, R. Causes and consequences of sperm mitochondrial dysfunction. Andrologia, 2021, 53(1), e13666. doi: 10.1111/and.13666 PMID: 32510691
  55. Wang, W.; Zhao, F.; Ma, X.; Perry, G.; Zhu, X. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: Recent advances. Mol. Neurodegener., 2020, 15(1), 30. doi: 10.1186/s13024-020-00376-6 PMID: 32471464
  56. Stojakovic, A.; Trushin, S.; Sheu, A.; Khalili, L.; Chang, S.Y.; Li, X.; Christensen, T.; Salisbury, J.L.; Geroux, R.E.; Gateno, B.; Flannery, P.J.; Dehankar, M.; Funk, C.C.; Wilkins, J.; Stepanova, A.; O’Hagan, T.; Galkin, A.; Nesbitt, J.; Zhu, X.; Tripathi, U.; Macura, S.; Tchkonia, T.; Pirtskhalava, T.; Kirkland, J.L.; Kudgus, R.A.; Schoon, R.A.; Reid, J.M.; Yamazaki, Y.; Kanekiyo, T.; Zhang, S.; Nemutlu, E.; Dzeja, P.; Jaspersen, A.; Kwon, Y.I.C.; Lee, M.K.; Trushina, E. Partial inhibition of mitochondrial complex I ameliorates Alzheimer’s disease pathology and cognition in APP/PS1 female mice. Commun. Biol., 2021, 4(1), 61. doi: 10.1038/s42003-020-01584-y PMID: 33420340
  57. Belosludtsev, K.N.; Sharipov, R.R.; Boyarkin, D.P.; Belosludtseva, N.V.; Dubinin, M.V.; Krasilnikova, I.A.; Bakaeva, Z.V.; Zgodova, A.E.; Pinelis, V.G.; Surin, A.M. The effect of DS16570511, a new inhibitor of mitochondrial calcium uniporter, on calcium homeostasis, metabolism, and functional state of cultured cortical neurons and isolated brain mitochondria. Biochim. Biophys. Acta, Gen. Subj., 2021, 1865(5), 129847. doi: 10.1016/j.bbagen.2021.129847 PMID: 33453305
  58. Carafoli, E. Historical review: Mitochondria and calcium: Ups and downs of an unusual relationship. Trends Biochem. Sci., 2003, 28(4), 175-181. doi: 10.1016/S0968-0004(03)00053-7 PMID: 12713900
  59. Zeb, A.; Kim, D.; Alam, S.; Son, M.; Kumar, R.; Rampogu, S.; Parameswaran, S.; Shelake, R.; Rana, R.; Parate, S.; Kim, J.Y.; Lee, K. Computational simulations identify pyrrolidine-2, 3-dione derivatives as novel inhibitors of Cdk5/p25 complex to attenuate Alzheimer’s pathology. J. Clin. Med., 2019, 8(5), 746. doi: 10.3390/jcm8050746 PMID: 31137734
  60. Bonora, M.; Giorgi, C.; Pinton, P. Molecular mechanisms and consequences of mitochondrial permeability transition. Nat. Rev. Mol. Cell Biol., 2022, 23, 266-285.
  61. Quintana, D.D.; Garcia, J.A.; Anantula, Y.; Rellick, S.L.; Engler-Chiurazzi, E.B.; Sarkar, S.N.; Brown, C.M.; Simpkins, J.W. Amyloid-β causes mitochondrial dysfunction via a Ca 2+-driven upregulation of oxidative phosphorylation and superoxide production in cerebrovascular endothelial cells. J. Alzheimers Dis., 2020, 75(1), 119-138. doi: 10.3233/JAD-190964 PMID: 32250296
  62. Filippone, A.; Esposito, E.; Mannino, D.; Lyssenko, N.; Praticò, D. The contribution of altered neuronal autophagy to neurodegeneration. Pharmacol. Ther., 2022, 238, 108178. doi: 10.1016/j.pharmthera.2022.108178 PMID: 35351465
  63. Sorrentino, V.; Romani, M.; Mouchiroud, L.; Beck, J.S.; Zhang, H.; D’Amico, D.; Moullan, N.; Potenza, F.; Schmid, A.W.; Rietsch, S.; Counts, S.E.; Auwerx, J. Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity. Nature, 2017, 552(7684), 187-193. doi: 10.1038/nature25143 PMID: 29211722
  64. Van Skike, C.E.; Lin, A.L.; Roberts Burbank, R.; Halloran, J.J.; Hernandez, S.F.; Cuvillier, J.; Soto, V.Y.; Hussong, S.A.; Jahrling, J.B.; Javors, M.A.; Hart, M.J.; Fischer, K.E.; Austad, S.N.; Galvan, V. mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging. Aging Cell, 2020, 19(1), e13057. doi: 10.1111/acel.13057 PMID: 31693798
  65. Zhang, W.; Xu, C.; Sun, J.; Shen, H.M.; Wang, J.; Yang, C. Impairment of the autophagy-lysosomal pathway in Alzheimer’s diseases: Pathogenic mechanisms and therapeutic potential. Acta Pharm. Sin. B, 2022, 12(3), 1019-1040. doi: 10.1016/j.apsb.2022.01.008 PMID: 35530153
  66. Pradeepkiran, J.A.; Hindle, A.; Kshirsagar, S.; Reddy, P.H. Are mitophagy enhancers therapeutic targets for Alzheimer’s disease? Biomed. Pharmacother., 2022, 149, 112918. doi: 10.1016/j.biopha.2022.112918 PMID: 35585708
  67. Nazam, N.; Farhana, A.; Shaikh, S. Recent advances in Alzheimer’s disease in relation to cholinesterase inhibitors and NMDA receptor antagonists, autism spectrum disorder and Alzheimer's disease., 2021, 135-151.
  68. Chiang, T.I.; Yu, Y.H.; Lin, C.H.; Lane, H.Y. Novel biomarkers of Alzheimer’s disease: Based upon N-methyl-d-aspartate receptor hypoactivation and oxidative stress. Clin. Psychopharmacol. Neurosci., 2021, 19(3), 423-433. doi: 10.9758/cpn.2021.19.3.423 PMID: 34294612
  69. Cheng, Y.J.; Lin, C.H.; Lane, H.Y. Involvement of cholinergic, adrenergic, and glutamatergic network modulation with cognitive dysfunction in Alzheimer’s disease. Int. J. Mol. Sci., 2021, 22(5), 2283. doi: 10.3390/ijms22052283 PMID: 33668976
  70. Nguyen, V.T.T.; Sallbach, J.; dos Santos Guilherme, M.; Endres, K. Influence of acetylcholine esterase inhibitors and memantine, clinically approved for Alzheimer’s dementia treatment, on intestinal properties of the mouse. Int. J. Mol. Sci., 2021, 22(3), 1015. doi: 10.3390/ijms22031015 PMID: 33498392
  71. Grundman, M.; Delaney, P.; Delaney, P. Antioxidant strategies for Alzheimer’s disease. Proc. Nutr. Soc., 2002, 61(2), 191-202. doi: 10.1079/PNS2002146 PMID: 12133201
  72. Malty, R.H.; Jessulat, M.; Jin, K.; Musso, G.; Vlasblom, J.; Phanse, S.; Zhang, Z.; Babu, M. Mitochondrial targets for pharmacological intervention in human disease. J. Proteome Res., 2015, 14(1), 5-21. doi: 10.1021/pr500813f PMID: 25367773
  73. Wang, X.; Su, B.; Zheng, L.; Perry, G.; Smith, M.A.; Zhu, X. The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease. J. Neurochem., 2009, 109(Suppl. 1), 153-159. doi: 10.1111/j.1471-4159.2009.05867.x PMID: 19393022
  74. Rahman, M.A.; Bishayee, K.; Huh, S.O. Angelica polymorpha maxim induces apoptosis of human SH-SY5Y neuroblastoma cells by regulating an intrinsic caspase pathway. Mol. Cells, 2016, 39(2), 119-128. doi: 10.14348/molcells.2016.2232 PMID: 26674967
  75. Kwon, Y.H.; Bishayee, K.; Rahman, A.; Hong, J.S.; Lim, S.S.; Huh, S.O. Morus alba accumulates reactive oxygen species to initiate apoptosis via FOXO-caspase 3-dependent pathway in neuroblastoma cells. Mol. Cells, 2015, 38(7), 630-637. doi: 10.14348/molcells.2015.0030 PMID: 25921607
  76. Rahman, M.A.; Hong, J.S.; Huh, S.O. Antiproliferative properties of Saussurea lappa Clarke root extract in SH-SY5Y neuroblastoma cells via intrinsic apoptotic pathway. Anim. Cells Syst., 2015, 19(2), 119-126. doi: 10.1080/19768354.2015.1008041
  77. Rahman, M.A.; Yang, H.; Kim, N.H.; Huh, S.O. Induction of apoptosis by Dioscorea nipponica Makino extracts in human SH-SY5Y neuroblastoma cells via mitochondria-mediated pathway. Anim. Cells Syst., 2014, 18(1), 41-51. doi: 10.1080/19768354.2014.880372
  78. Rahman, M.A.; Yang, H.; Lim, S.S.; Huh, S.O. Apoptotic effects of melandryum firmum root extracts in human SH-SY5Y neuroblastoma cells. Exp. Neurobiol., 2013, 22(3), 208-213. doi: 10.5607/en.2013.22.3.208 PMID: 24167415
  79. Rahman, M.A.; Kim, N.H.; Huh, S.O. Cytotoxic effect of gambogic acid on SH-SY5Y neuroblastoma cells is mediated by intrinsic caspase-dependent signaling pathway. Mol. Cell. Biochem., 2013, 377(1-2), 187-196. doi: 10.1007/s11010-013-1584-z PMID: 23404459
  80. Rahman, M.A.; Kim, N.H.; Kim, S.H.; Oh, S.M.; Huh, S.O. Antiproliferative and cytotoxic effects of resveratrol in mitochondria-mediated apoptosis in rat b103 neuroblastoma cells. Korean J. Physiol. Pharmacol., 2012, 16(5), 321-326. doi: 10.4196/kjpp.2012.16.5.321 PMID: 23118555
  81. Ataur Rahman, M.; Kim, N.H.; Yang, H.; Huh, S.O. Angelicin induces apoptosis through intrinsic caspase-dependent pathway in human SH-SY5Y neuroblastoma cells. Mol. Cell. Biochem., 2012, 369(1-2), 95-104. doi: 10.1007/s11010-012-1372-1 PMID: 22766766
  82. Hannan, M.A.; Dash, R.; Haque, M.N.; Mohibbullah, M.; Sohag, A.A.; Rahman, M.A.; Uddin, M.J.; Alam, M.; Moon, I. Neuroprotective potentials of marine algae and their bioactive metabolites: Pharmacological insights and therapeutic advances. Mar. Drugs, 2020, 18, 347. doi: 10.3390/md18070347
  83. Rahman, M.A.; Rahman, M.R.; Zaman, T.; Uddin, M.S.; Islam, R.; Abdel-Daim, M.M.; Rhim, H. Emerging potential of naturally occurring autophagy modulators against neurodegeneration. Curr. Pharm. Des., 2020, 26(7), 772-779. doi: 10.2174/1381612826666200107142541 PMID: 31914904
  84. Rahman, M.A.; Saha, S.K.; Rahman, M.S.; Uddin, M.J.; Uddin, M.S.; Pang, M.G.; Rhim, H.; Cho, S.G. Molecular insights into therapeutic potential of autophagy modulation by natural products for cancer stem cells. Front. Cell Dev. Biol., 2020, 8, 283. doi: 10.3389/fcell.2020.00283
  85. Rahman, M.A.; Hwang, H.; Nah, S.Y.; Rhim, H. Gintonin stimulates autophagic flux in primary cortical astrocytes. J. Ginseng Res., 2020, 44(1), 67-78. doi: 10.1016/j.jgr.2018.08.004 PMID: 32148391
  86. Rahman, M.A.; Bishayee, K.; Sadra, A.; Huh, S.O. Oxyresveratrol activates parallel apoptotic and autophagic cell death pathways in neuroblastoma cells. Biochim. Biophys. Acta, Gen. Subj., 2017, 1861(2), 23-36. doi: 10.1016/j.bbagen.2016.10.025 PMID: 27815218
  87. Rahman, M.A.; Bishayee, K.; Habib, K.; Sadra, A.; Huh, S.O. 18α-Glycyrrhetinic acid lethality for neuroblastoma cells via de-regulating the Beclin-1/Bcl-2 complex and inducing apoptosis. Biochem. Pharmacol., 2016, 117, 97-112. doi: 10.1016/j.bcp.2016.08.006 PMID: 27520483
  88. Jangra, A.; Arora, M.K.; Kisku, A.; Sharma, S. The multifaceted role of mangiferin in health and diseases: A review. Advn Tradi Med., 2021, 21(4), 619-643. doi: 10.1007/s13596-020-00471-5
  89. Sarikurkcu, C.; Sahinler, S.S.; Ceylan, O.; Tepe, B. Onosma pulchra: Phytochemical composition, antioxidant, skin-whitening and anti-diabetic activity. Ind. Crop. Prod, 2020, 154.
  90. Franco, R.; Navarro, G.; Martinez-Pinilla, E. Hormetic and mitochondria-related mechanisms of antioxidant action of phytochemicals. Antioxidants-Basel, 2019, 8, 373. doi: 10.3390/antiox8090373
  91. Zhu, F.; Du, B.; Xu, B. Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: A review. Crit. Rev. Food Sci. Nutr., 2018, 58(8), 1260-1270. doi: 10.1080/10408398.2016.1251390 PMID: 28605204
  92. Vaiserman, A.; Koliada, A.; Lushchak, O. Neuroinflammation in pathogenesis of Alzheimer’s disease: Phytochemicals as potential therapeutics. Mech. Ageing Dev., 2020, 189, 111259. doi: 10.1016/j.mad.2020.111259 PMID: 32450086
  93. Li, Y.; Zhang, J.; Wan, J.; Liu, A.; Sun, J. Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: A potential therapeutic molecule for Alzheimer’s disease. Biomed. Pharmacother., 2020, 132, 110887. doi: 10.1016/j.biopha.2020.110887 PMID: 33254429
  94. Reddy, P.H.; Manczak, M.; Yin, X.; Grady, M.C.; Mitchell, A.; Kandimalla, R.; Kuruva, C.S. Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer’s disease. J. Investig. Med., 2016, 64(8), 1220-1234. doi: 10.1136/jim-2016-000240 PMID: 27521081
  95. Wang, D.M.; Li, S.Q.; Wu, W.L.; Zhu, X.Y.; Wang, Y.; Yuan, H.Y. Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer’s disease. Neurochem. Res., 2014, 39(8), 1533-1543. doi: 10.1007/s11064-014-1343-x PMID: 24893798
  96. Paula, P.C.; Angelica, M.S.G.; Luis, C.H.; Gloria, P.C.G. Preventive effect of quercetin in a triple transgenic Alzheimer's disease mice model. Molecules, 2019, 24. doi: 10.3390/molecules24122287
  97. Sabogal-Guáqueta, A.M.; Muñoz-Manco, J.I.; Ramírez-Pineda, J.R.; Lamprea-Rodriguez, M.; Osorio, E.; Cardona-Gómez, G.P. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology, 2015, 93, 134-145. doi: 10.1016/j.neuropharm.2015.01.027 PMID: 25666032
  98. Román, G.C.; Jackson, R.E.; Gadhia, R.; Román, A.N.; Reis, J. Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease. Rev. Neurol. (Paris), 2019, 175(10), 724-741. doi: 10.1016/j.neurol.2019.08.005 PMID: 31521398
  99. Sohel, M.; Biswas, P.; Al Amin, M.; Hossain, M.A.; Sultana, H.; Dey, D.; Aktar, S.; Setu, A.; Khan, M.S.; Paul, P.; Islam, M.N.; Rahman, M.A.; Kim, B.; Al Mamun, A. Genistein, a potential phytochemical against breast cancer treatment-Insight into the molecular mechanisms. Processes (Basel), 2022, 10(2), 415. doi: 10.3390/pr10020415
  100. Uddin, M.S.; Kabir, M.T. Emerging signal regulating potential of genistein against Alzheimer’s disease: A promising molecule of interest. Front. Cell Dev. Biol., 2019, 7, 197. doi: 10.3389/fcell.2019.00197 PMID: 31620438
  101. Pierzynowska, K.; Podlacha, M.; Gaffke, L.; Majkutewicz, I.; Mantej, J.; Węgrzyn, A.; Osiadły, M.; Myślińska, D.; Węgrzyn, G. Autophagy-dependent mechanism of genistein-mediated elimination of behavioral and biochemical defects in the rat model of sporadic Alzheimer’s disease. Neuropharmacology, 2019, 148, 332-346. doi: 10.1016/j.neuropharm.2019.01.030 PMID: 30710571
  102. Rassu, G.; Porcu, E.; Fancello, S.; Obinu, A.; Senes, N.; Galleri, G.; Migheli, R.; Gavini, E.; Giunchedi, P. Intranasal delivery of genistein-loaded nanoparticles as a potential preventive system against neurodegenerative disorders. Pharmaceutics, 2018, 11(1), 8. doi: 10.3390/pharmaceutics11010008 PMID: 30597930
  103. Jo, D.S.; Shin, D.W.; Park, S.J.; Bae, J.E.; Kim, J.B.; Park, N.Y.; Kim, J.S.; Oh, J.S.; Shin, J.W.; Cho, D.H. Attenuation of Aβ toxicity by promotion of mitochondrial fusion in neuroblastoma cells by liquiritigenin. Arch. Pharm. Res., 2016, 39(8), 1137-1143. doi: 10.1007/s12272-016-0780-2 PMID: 27515055
  104. Valles, S.L.; Dolz-Gaiton, P.; Gambini, J.; Borras, C.; LLoret, A.; Pallardo, F.V.; Viña, J. Estradiol or genistein prevent Alzheimer’s disease-associated inflammation correlating with an increase PPARγ expression in cultured astrocytes. Brain Res., 2010, 1312, 138-144. doi: 10.1016/j.brainres.2009.11.044 PMID: 19948157
  105. Parrado-Fernández, C.; Sandebring-Matton, A.; Rodriguez-Rodriguez, P.; Aarsland, D.; Cedazo-Mínguez, A. Anthocyanins protect from complex I inhibition and APPswe mutation through modulation of the mitochondrial fission/fusion pathways. Biochim. Biophys. Acta Mol. Basis Dis., 2016, 1862(11), 2110-2118. doi: 10.1016/j.bbadis.2016.08.002 PMID: 27498295
  106. Godoy, J.A.; Lindsay, C.B.; Quintanilla, R.A.; Carvajal, F.J.; Cerpa, W.; Inestrosa, N.C. Quercetin exerts differential neuroprotective effects against H2O2 and Aβ aggregates in hippocampal neurons: The role of mitochondria. Mol. Neurobiol., 2017, 54(9), 7116-7128. doi: 10.1007/s12035-016-0203-x PMID: 27796749
  107. Kwon, S.H.; Ma, S.X.; Hwang, J.Y.; Lee, S.Y.; Jang, C.G. Involvement of the Nrf2/HO-1 signaling pathway in sulfuretin-induced protection against amyloid beta25–35 neurotoxicity. Neuroscience, 2015, 304, 14-28. doi: 10.1016/j.neuroscience.2015.07.030 PMID: 26192096
  108. Chesser, A.S.; Ganeshan, V.; Yang, J.; Johnson, G.V.W. Epigallocatechin-3-gallate enhances clearance of phosphorylated tau in primary neurons. Nutr. Neurosci., 2016, 19(1), 21-31. doi: 10.1179/1476830515Y.0000000038 PMID: 26207957
  109. Huang, L.; Chen, C.; Zhang, X.; Li, X.; Chen, Z.; Yang, C.; Liang, X.; Zhu, G.; Xu, Z. Neuroprotective effect of curcumin against cerebral ischemia-reperfusion via mediating autophagy and inflammation. J. Mol. Neurosci., 2018, 64(1), 129-139. doi: 10.1007/s12031-017-1006-x PMID: 29243061
  110. Sousa, J.C.; Santana, A.C.F.; Magalhães, G.J.P. Resveratrol in Alzheimer’s disease: A review of pathophysiology and therapeutic potential. Arq. Neuropsiquiatr., 2020, 78(8), 501-511. doi: 10.1590/0004-282x20200010 PMID: 32520230
  111. Qi, G.; Mi, Y.; Wang, Y.; Li, R.; Huang, S.; Li, X.; Liu, X. Neuroprotective action of tea polyphenols on oxidative stress-induced apoptosis through the activation of the TrkB/CREB/BDNF pathway and Keap1/Nrf2 signaling pathway in SH-SY5Y cells and mice brain. Food Funct., 2017, 8(12), 4421-4432. doi: 10.1039/C7FO00991G PMID: 29090295
  112. Yao, X.; Jiang, H.; NanXu, Y.; Piao, X.; Gao, Q.; Kim, N.H. Kaempferol attenuates mitochondrial dysfunction and oxidative stress induced by H2O2 during porcine embryonic development. Theriogenology, 2019, 135, 174-180. doi: 10.1016/j.theriogenology.2019.06.013 PMID: 31226607
  113. Korolchuk, V.I.; Miwa, S.; Carroll, B.; von Zglinicki, T. Mitochondria in cell senescence: Is mitophagy the weakest link? EBioMedicine, 2017, 21, 7-13. doi: 10.1016/j.ebiom.2017.03.020 PMID: 28330601
  114. Ashrafi, G.; Schwarz, T.L. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ., 2013, 20(1), 31-42. doi: 10.1038/cdd.2012.81 PMID: 22743996
  115. Li, X.; Alafuzoff, I.; Soininen, H.; Winblad, B.; Pei, J.J. Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer’s disease brain. FEBS J., 2005, 272(16), 4211-4220. doi: 10.1111/j.1742-4658.2005.04833.x PMID: 16098202
  116. Perluigi, M.; Di Domenico, F.; Butterfield, D.A. mTOR signaling in aging and neurodegeneration: At the crossroad between metabolism dysfunction and impairment of autophagy. Neurobiol. Dis., 2015, 84, 39-49. doi: 10.1016/j.nbd.2015.03.014 PMID: 25796566
  117. Pan, T.; Rawal, P.; Wu, Y.; Xie, W.; Jankovic, J.; Le, W. Rapamycin protects against rotenone-induced apoptosis through autophagy induction. Neuroscience, 2009, 164(2), 541-551. doi: 10.1016/j.neuroscience.2009.08.014 PMID: 19682553
  118. Morton, H.; Kshirsagar, S.; Orlov, E.; Bunquin, L.E.; Sawant, N.; Boleng, L.; George, M.; Basu, T.; Ramasubramanian, B.; Pradeepkiran, J.A.; Kumar, S.; Vijayan, M.; Reddy, A.P.; Reddy, P.H. Defective mitophagy and synaptic degeneration in Alzheimer’s disease: Focus on aging, mitochondria and synapse. Free Radic. Biol. Med., 2021, 172, 652-667. doi: 10.1016/j.freeradbiomed.2021.07.013 PMID: 34246776
  119. Wang, W.W.; Han, R.; He, H.J.; Wang, Z.; Luan, X.Q.; Li, J.; Feng, L.; Chen, S.Y.; Aman, Y.; Xie, C.L. Delineating the role of mitophagy inducers for Alzheimer disease patients. Aging Dis., 2021, 12(3), 852-867. doi: 10.14336/AD.2020.0913 PMID: 34094647
  120. Jurcau, A. Insights into the pathogenesis of neurodegenerative diseases: Focus on mitochondrial dysfunction and oxidative stress. Int. J. Mol. Sci., 2021, 22(21), 11847. doi: 10.3390/ijms222111847 PMID: 34769277
  121. Friedland-Leuner, K.; Stockburger, C.; Denzer, I.; Eckert, G.P.; Müller, W.E. Mitochondrial dysfunction. Prog. Mol. Biol. Transl. Sci., 2014, 127, 183-210. doi: 10.1016/B978-0-12-394625-6.00007-6 PMID: 25149218
  122. von Gunten, A.; Schlaefke, S.; Überla, K. Efficacy of Ginkgo biloba extract EGb 761 ® in dementia with behavioural and psychological symptoms: A systematic review. World J. Biol. Psychiatry, 2016, 17(8), 622-633. doi: 10.3109/15622975.2015.1066513 PMID: 26223956
  123. Heckmann, B.L.; Teubner, B.J.; Tummers, B.; Boada-Romero, E.; Harris, L.; Yang, M.; Guy, C.S.; Zakharenko, S.S.; Green, D.R. LC3-associated endocytosis facilitates β-amyloid clearance and mitigates neurodegeneration in murine Alzheimer’s disease. Cell, 2019, 178, 536-551.
  124. Fang, E.F.; Hou, Y.; Palikaras, K.; Adriaanse, B.A.; Kerr, J.S.; Yang, B.; Lautrup, S.; Hasan-Olive, M.M.; Caponio, D.; Dan, X.; Rocktäschel, P.; Croteau, D.L.; Akbari, M.; Greig, N.H.; Fladby, T.; Nilsen, H.; Cader, M.Z.; Mattson, M.P.; Tavernarakis, N.; Bohr, V.A. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat. Neurosci., 2019, 22(3), 401-412. doi: 10.1038/s41593-018-0332-9 PMID: 30742114
  125. Yeong, K.Y.; Berdigaliyev, N.; Chang, Y. Sirtuins and their implications in neurodegenerative diseases from a drug discovery perspective. ACS Chem. Neurosci., 2020, 11(24), 4073-4091. doi: 10.1021/acschemneuro.0c00696 PMID: 33280374
  126. Zhang, Z.; Shen, Q.; Wu, X.; Zhang, D.; Xing, D. Activation of PKA/SIRT1 signaling pathway by photobiomodulation therapy reduces Aβ levels in Alzheimer’s disease models. Aging Cell, 2020, 19(1), e13054. doi: 10.1111/acel.13054 PMID: 31663252
  127. Chu, C.Q.; Yu, L.; Qi, G.; Mi, Y.S.; Wu, W.Q.; Lee, Y.; Zhai, Q.X.; Tian, F.W.; Chen, W. Can dietary patterns prevent cognitive impairment and reduce Alzheimer’s disease risk: Exploring the underlying mechanisms of effects. Neurosci. Biobehav. Rev., 2022, 135, 104556. doi: 10.1016/j.neubiorev.2022.104556 PMID: 35122783
  128. Alemany-Cosme, E.; Sáez-González, E.; Moret, I.; Mateos, B.; Iborra, M.; Nos, P.; Sandoval, J.; Beltrán, B. Oxidative stress in the pathogenesis of crohn’s disease and the interconnection with immunological response, microbiota, external environmental factors, and epigenetics. Antioxidants, 2021, 10(1), 64. doi: 10.3390/antiox10010064 PMID: 33430227
  129. Hadrich, F.; Chamkha, M.; Sayadi, S. Protective effect of olive leaves phenolic compounds against neurodegenerative disorders: Promising alternative for Alzheimer and Parkinson diseases modulation. Food Chem. Toxicol., 2022, 159, 112752. doi: 10.1016/j.fct.2021.112752 PMID: 34871668
  130. Abdallah, I.M.; Al-Shami, K.M.; Yang, E.; Wang, J.; Guillaume, C.; Kaddoumi, A. Oleuropein-rich olive leaf extract attenuates neuroinflammation in the Alzheimer’s disease mouse model. ACS Chem. Neurosci., 2022, 13, 1002-1013.
  131. Sridharan, B.; Lee, M.J. Ketogenic diet: A promising neuroprotective composition for managing Alzheimer’s diseases and its pathological mechanisms. Curr. Mol. Med., 2022, 22(7), 640-656. doi: 10.2174/1566524021666211004104703 PMID: 34607541
  132. Napoleão, A.; Fernandes, L.; Miranda, C.; Marum, A.P. Effects of calorie restriction on health span and insulin resistance: Classic calorie restriction diet vs. ketosis-inducing diet. Nutrients, 2021, 13(4), 1302. doi: 10.3390/nu13041302 PMID: 33920973
  133. Misrani, A.; Tabassum, S.; Yang, L. Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease. Front. Aging Neurosci., 2021, 13, 617588. doi: 10.3389/fnagi.2021.617588 PMID: 33679375
  134. Nisoli, E.; Tonello, C.; Cardile, A.; Cozzi, V.; Bracale, R.; Tedesco, L.; Falcone, S.; Valerio, A.; Cantoni, O.; Clementi, E.; Moncada, S.; Carruba, M.O. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science, 2005, 310(5746), 314-317. doi: 10.1126/science.1117728 PMID: 16224023
  135. Bo, H.; Kang, W.; Jiang, N.; Wang, X.; Zhang, Y.; Ji, L.L. Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase. Oxid. Med. Cell. Longev., 2014, 2014, 1-14. doi: 10.1155/2014/834502 PMID: 25538817
  136. Klein, C.P.; Hoppe, J.B.; Saccomori, A.B.; dos Santos, B.G.; Sagini, J.P.; Crestani, M.S.; August, P.M.; Hözer, R.M.; Grings, M.; Parmeggiani, B.; Leipnitz, G.; Navas, P.; Salbego, C.G.; Matté, C. Physical exercise during pregnancy prevents cognitive impairment induced by amyloid-β in adult offspring rats. Mol. Neurobiol., 2019, 56(3), 2022-2038. doi: 10.1007/s12035-018-1210-x PMID: 29982984
  137. Longobardi, A.; Nicsanu, R.; Bellini, S.; Squitti, R.; Catania, M.; Tiraboschi, P.; Saraceno, C.; Ferrari, C.; Zanardini, R.; Binetti, G.; Di Fede, G.; Benussi, L.; Ghidoni, R. Cerebrospinal fluid EV concentration and size are altered in Alzheimer’s disease and dementia with lewy bodies. Cells, 2022, 11(3), 462. doi: 10.3390/cells11030462 PMID: 35159272
  138. Yokoyama, H.; Okazaki, K.; Imai, D.; Yamashina, Y.; Takeda, R.; Naghavi, N.; Ota, A.; Hirasawa, Y.; Miyagawa, T. The effect of cognitive-motor dual-task training on cognitive function and plasma amyloid β peptide 42/40 ratio in healthy elderly persons: A randomized controlled trial. BMC Geriatr., 2015, 15(1), 60. doi: 10.1186/s12877-015-0058-4 PMID: 26018225
  139. Zhang, S.; Lachance, B.B.; Mattson, M.P.; Jia, X. Glucose metabolic crosstalk and regulation in brain function and diseases. Prog. Neurobiol., 2021, 204, 102089. doi: 10.1016/j.pneurobio.2021.102089 PMID: 34118354
  140. Terzo, S.; Amato, A.; Mulè, F. From obesity to Alzheimer’s disease through insulin resistance. J. Diabetes Complications, 2021, 35(11), 108026. doi: 10.1016/j.jdiacomp.2021.108026 PMID: 34454830
  141. De Felice, F.G.; Gonçalves, R.A.; Ferreira, S.T. Impaired insulin signalling and allostatic load in Alzheimer disease. Nat. Rev. Neurosci., 2022, 23(4), 215-230. doi: 10.1038/s41583-022-00558-9 PMID: 35228741
  142. Hallschmid, M. Intranasal insulin for Alzheimer’s disease. CNS Drugs, 2021, 35(1), 21-37. doi: 10.1007/s40263-020-00781-x PMID: 33515428
  143. Chadha, S.; Behl, T.; Sehgal, A.; Kumar, A.; Bungau, S. Exploring the role of mitochondrial proteins as molecular target in Alzheimer’s disease. Mitochondrion, 2021, 56, 62-72. doi: 10.1016/j.mito.2020.11.008 PMID: 33221353
  144. Athar, T.; Al Balushi, K.; Khan, S.A. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Mol. Biol. Rep., 2021, 48(7), 5629-5645. doi: 10.1007/s11033-021-06512-9 PMID: 34181171
  145. Austad, S.N.; Ballinger, S.; Buford, T.W.; Carter, C.S.; Smith, D.L., Jr; Darley-Usmar, V.; Zhang, J. Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer’s disease. Acta Pharm. Sin. B, 2022, 12(2), 511-310. PMID: 35256932
  146. Nguyen, T.T.; Nguyen, T.T.D.; Nguyen, T.K.O.; Vo, T.K.; Vo, V.G. Advances in developing therapeutic strategies for Alzheimer’s disease. Biomed. Pharmacother., 2021, 139, 111623. doi: 10.1016/j.biopha.2021.111623 PMID: 33915504
  147. Han, Y.; Chu, X.; Cui, L.; Fu, S.; Gao, C.; Li, Y.; Sun, B. Neuronal mitochondria-targeted therapy for Alzheimer’s disease by systemic delivery of resveratrol using dual-modified novel biomimetic nanosystems. Drug Deliv., 2020, 27(1), 502-518. doi: 10.1080/10717544.2020.1745328 PMID: 32228100
  148. Ordóñez-Gutiérrez, L.; Re, F.; Bereczki, E.; Ioja, E.; Gregori, M.; Andersen, A.J.; Antón, M.; Moghimi, S.M.; Pei, J.J.; Masserini, M.; Wandosell, F. Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice. Nanomedicine, 2015, 11(2), 421-430. doi: 10.1016/j.nano.2014.09.015 PMID: 25461285
  149. Kryscio, R.J.; Abner, E.L.; Caban-Holt, A.; Lovell, M.; Goodman, P.; Darke, A.K.; Yee, M.; Crowley, J.; Schmitt, F.A. Association of antioxidant supplement use and dementia in the prevention of Alzheimer’s disease by vitamin E and selenium trial (PREADViSE). JAMA Neurol., 2017, 74(5), 567-573. doi: 10.1001/jamaneurol.2016.5778 PMID: 28319243
  150. Rahman, M.A.; Cho, Y.; Nam, G.; Rhim, H. Antioxidant compound, oxyresveratrol, inhibits APP production through the AMPK/ULK1/mTOR-mediated autophagy pathway in mouse cortical astrocytes. Antioxidants, 2021, 10(3), 408. doi: 10.3390/antiox10030408 PMID: 33800526
  151. Luo, Q.; Lin, Y.X.; Yang, P.P.; Wang, Y.; Qi, G.B.; Qiao, Z.Y.; Li, B.N.; Zhang, K.; Zhang, J.P.; Wang, L.; Wang, H. A self-destructive nanosweeper that captures and clears amyloid β-peptides. Nat. Commun., 2018, 9(1), 1802. doi: 10.1038/s41467-018-04255-z PMID: 29728565
  152. Wang, S.; Zheng, J.; Ma, L.; Petersen, R.B.; Xu, L.; Huang, K. Inhibiting protein aggregation with nanomaterials: The underlying mechanisms and impact factors. Biochim. Biophys. Acta, Gen. Subj., 2022, 1866(2), 130061. doi: 10.1016/j.bbagen.2021.130061 PMID: 34822925
  153. Nguyen, T.T.; Vo, T.K.; Vo, G.V. Therapeutic strategies and nano-drug delivery applications in management of aging Alzheimer’s disease. Rev. New Drug Targets in Age-Related Disorders, 2021, 183-198.
  154. Gobbi, M.; Re, F.; Canovi, M.; Beeg, M.; Gregori, M.; Sesana, S.; Sonnino, S.; Brogioli, D.; Musicanti, C.; Gasco, P.; Salmona, M.; Masserini, M.E. Lipid-based nanoparticles with high binding affinity for amyloid-β1-42 peptide. Biomaterials, 2010, 31(25), 6519-6529. doi: 10.1016/j.biomaterials.2010.04.044 PMID: 20553982
  155. Poudel, P.; Park, S. Recent advances in the treatment of Alzheimer’s disease using nanoparticle-based drug delivery systems. Pharmaceutics, 2022, 14, 835.
  156. Ali, T.; Kim, M.J.; Rehman, S.U.; Ahmad, A.; Kim, M.O. Anthocyanin-loaded PEG-gold nanoparticles enhanced the neuroprotection of anthocyanins in an Aβ1-42 mouse model of Alzheimer’s disease. Mol. Neurobiol., 2017, 54(8), 6490-6506. doi: 10.1007/s12035-016-0136-4 PMID: 27730512
  157. Liu, X.; An, C.; Jin, P.; Liu, X.; Wang, L. Protective effects of cationic bovine serum albumin-conjugated PEGylated tanshinone IIA nanoparticles on cerebral ischemia. Biomaterials, 2013, 34(3), 817-830. doi: 10.1016/j.biomaterials.2012.10.017 PMID: 23111336
  158. Lohan, S.; Raza, K.; Mehta, S.K.; Bhatti, G.K.; Saini, S.; Singh, B. Anti-Alzheimer’s potential of berberine using surface decorated multi-walled carbon nanotubes: A preclinical evidence. Int. J. Pharm., 2017, 530(1-2), 263-278. doi: 10.1016/j.ijpharm.2017.07.080 PMID: 28774853
  159. Mirsadeghi, S.; Shanehsazzadeh, S.; Atyabi, F.; Dinarvand, R. Effect of PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) under magnetic field on amyloid beta fibrillation process. Mater. Sci. Eng. C, 2016, 59, 390-397. doi: 10.1016/j.msec.2015.10.026 PMID: 26652388
  160. Conti, E.; Gregori, M.; Radice, I.; Da Re, F.; Grana, D.; Re, F.; Salvati, E.; Masserini, M.; Ferrarese, C.; Zoia, C.P.; Tremolizzo, L. Multifunctional liposomes interact with Abeta in human biological fluids: Therapeutic implications for Alzheimer’s disease. Neurochem. Int., 2017, 108, 60-65. doi: 10.1016/j.neuint.2017.02.012 PMID: 28238790
  161. Karimzadeh, M.; Rashidi, L.; Ganji, F. Mesoporous silica nanoparticles for efficient rivastigmine hydrogen tartrate delivery into SY5Y cells. Drug Dev. Ind. Pharm., 2017, 43(4), 628-636. doi: 10.1080/03639045.2016.1275668 PMID: 28043167
  162. Misra, S.; Chopra, K.; Sinha, V.R.; Medhi, B. Galantamine-loaded solid-lipid nanoparticles for enhanced brain delivery: Preparation, characterization, in vitro and in vivo evaluations. Drug Deliv., 2016, 23(4), 1434-1443. doi: 10.3109/10717544.2015.1089956 PMID: 26405825
  163. Li, H.; Luo, Y.; Derreumaux, P.; Wei, G. Carbon nanotube inhibits the formation of β-sheet-rich oligomers of the Alzheimer’s amyloid-β(16-22) peptide. Biophys. J., 2011, 101(9), 2267-2276. doi: 10.1016/j.bpj.2011.09.046 PMID: 22067167
  164. Liu, Z.; Gao, X.; Kang, T.; Jiang, M.; Miao, D.; Gu, G.; Hu, Q.; Song, Q.; Yao, L.; Tu, Y.; Chen, H.; Jiang, X.; Chen, J. B6 peptide-modified PEG-PLA nanoparticles for enhanced brain delivery of neuroprotective peptide. Bioconjug. Chem., 2013, 24(6), 997-1007. doi: 10.1021/bc400055h PMID: 23718945
  165. Karatas, H.; Aktas, Y.; Gursoy-Ozdemir, Y.; Bodur, E.; Yemisci, M.; Caban, S.; Vural, A.; Pinarbasli, O.; Capan, Y.; Fernandez-Megia, E.; Novoa-Carballal, R.; Riguera, R.; Andrieux, K.; Couvreur, P.; Dalkara, T. A nanomedicine transports a peptide caspase-3 inhibitor across the blood-brain barrier and provides neuroprotection. J. Neurosci., 2009, 29(44), 13761-13769. doi: 10.1523/JNEUROSCI.4246-09.2009 PMID: 19889988
  166. Villemagne, V.L.; Burnham, S.; Bourgeat, P.; Brown, B.; Ellis, K.A.; Salvado, O.; Szoeke, C.; Macaulay, S.L.; Martins, R.; Maruff, P.; Ames, D.; Rowe, C.C.; Masters, C.L. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurol., 2013, 12(4), 357-367. doi: 10.1016/S1474-4422(13)70044-9 PMID: 23477989
  167. Schaffhauser, H.; Mathiasen, J.R.; DiCamillo, A.; Huffman, M.J.; Lu, L.D.; McKenna, B.A.; Qian, J.; Marino, M.J. Dimebolin is a 5-HT6 antagonist with acute cognition enhancing activities. Biochem. Pharmacol., 2009, 78(8), 1035-1042. doi: 10.1016/j.bcp.2009.06.021 PMID: 19549510
  168. Burns, D.K.; Chiang, C.; Welsh-Bohmer, K.A.; Brannan, S.K.; Culp, M.; O’Neil, J.; Runyan, G.; Harrigan, P.; Plassman, B.L.; Lutz, M.; Lai, E.; Haneline, S.; Yarnall, D.; Yarbrough, D.; Metz, C.; Ponduru, S.; Sundseth, S.; Saunders, A.M. The TOMMORROW study: Design of an Alzheimer’s disease delay‐of‐onset clinical trial. Alzheimers Dement. (N. Y.), 2019, 5(1), 661-670. doi: 10.1016/j.trci.2019.09.010 PMID: 31720367
  169. Swerdlow, R.H.; Bothwell, R.; Hutfles, L.; Burns, J.M.; Reed, G.A. Tolerability and pharmacokinetics of oxaloacetate 100mg capsules in Alzheimer’s subjects. BBA Clin., 2016, 5, 120-123. doi: 10.1016/j.bbacli.2016.03.005 PMID: 27051598
  170. Mani, S.; Swargiary, G.; Singh, M.; Agarwal, S.; Dey, A.; Ojha, S.; Jha, N.K. Mitochondrial defects: An emerging theranostic avenue towards Alzheimer’s associated dysregulations. Life Sci., 2021, 285, 119985. doi: 10.1016/j.lfs.2021.119985 PMID: 34592237

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