The influence of the liposomal form of curcumin and microRNA on the course of Alzheimer’s disease
Abstract
Infiltration of inflammatory cytokines, oxidative stress, and chronic inflammation are associated with the onset and progression of neurodegenerative and oncological diseases. For this reason, treatment with drugs with antioxidant and anti-inflammatory properties may be appropriate to prevent or slow the progression of these disorders. Alzheimer's disease is associated with the occurrence and progression of cerebral amyloidosis in the foci of cholinergic neurons of the neocortex and hippocampus. It is the neurons of the neocortex and hippocampus that suffer the most from the toxicity of Aβ oligomers, which subsequently form senile plaques, leading to the destruction of neuronal networks and the activation of nonspecific inflammation. Polyphenols, such as flavonoids, are characterised by potent antioxidant and anti-inflammatory properties. Curcumin exhibits a wide spectrum of pharmacological activity against many chronic diseases and is able not only to inhibit cell proliferation but also to induce apoptosis by modulating several pro-inflammatory factors. Curcumin’s bioavailability is limited by its low solubility in water, so loading curcumin into appropriate nanocarriers can improve its efficacy, local deposition and distribution. Targeted delivery of pharmaceutically active ingredients is a pressing issue and, given the significant results in proteome research, is emerging as a leading issue in the study of RNA regulatory mechanisms, in particular, the divergent functions of small RNAs (microRNAs). MicroRNAs are key modulators of the genome due to their ability to influence most of the genes that code for proteins in the body. Gene therapy regulates or blocks the overexpression of a single gene at the post-transcriptional level using the corresponding microRNA. The major unresolved problem in the applic a tion of microRNAs has been the targeted delivery of these molecules. Therefore, to address the challenge of targeted delivery of microRNA to the central nervous system, it is proposed to use administration via lipid-based delivery nanosystems. The review presents the main characteristics and mechanisms of action of curcumin and microRNA on the chronic inflammatory process that consistently accompanies the progression of amyloidosis, as well as their direct inhibitory effect on the excessive formation of β-amyloid peptides. It has been shown that microRNA miR-101 can specifically interact, via its “seed” region, with the messenger RNA of the amyloid precursor protein (AβPP), thereby repressing the overexpression of the AβPP gene and preventing its amyloidogenic processing.References
Antunes, L. M. G., Araujo, M. C. P., da Luz Dias, F., & Takahashi, C. S. (2005). Effects of H2O2, Fe2+ and Fe3+ on curcumin-induced chromosomal aberrations in CHO cells. Genetics and Molecular Biology, 28(1), 161–164.
Bao, W. D., Pang, P., Zhou, X. T., Hu, F., Xiong, W., Chen, K., Wang, J., Wang, F., Xie, D., Hu, Y. Z., Han, Z. T., Zhang, H. H., Wang, W. X., Nelson, P. T., Chen, J. G., Lu, Y., Man, H. Y., Liu, D., & Zhu, L. Q. (2021). Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer's disease. Cell Death and Differentiation, 28(5), 1548–1562.
Barbato, C., Pezzola, S., Caggiano, C., Antonelli, M., Frisone, P., Ciotti, M. T., & Ruberti, F. (2014). A lentiviral sponge for miR-101 regulates RanBP9 expression and amyloid precursor protein metabolism in hippocampal neurons. Frontiers of Cell Neuroscience, 8, 37.
Calvo-Rodriguez, M., Hou, S. S., Snyder, A. C., Kharitonova, E. K., Russ, A. N., Das, S., Fan, Z., Muzikansky, A., Garcia-Alloza, M., Serrano-Pozo, A., Hudry, E., & Bacskai, B. J. (2020). Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease. Nature Communications, 11(1), 2146.
Chainoglou, E., & Hadjipavlou-Litina, D. (2020). Curcumin in health and diseases: Alzheimer's disease and curcumin analogues, derivatives, and hybrids. International Journal of Molecular Sciences, 21(6), 1975.
Chan, M. M., Huang, H. I., Fenton, M. R., & Fong, D. (1998). In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochemical Pharmacology, 55(12), 1955–1962.
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018). The amyloid-β oligomer hypothesis: Beginning of the third decade. Journal of Alzheimer's Disease, 64(S1), S567–S610.
Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., Broich, K., Cavedo, E., Crutch, S., Dartigues, J.-F., Duyckaerts, C., Epelbaum, S., Frisoni, G. B., Gauthier, S., Genthon, R., Gouw, A., Habert, M.-O., Holtzman, D. M., Kivipelto, M., Lista, S., Molinuevo, J.-L., O'Bryant, S. E., Rabinovici, G. D., Rowe, C., Salloway, S., Schneider, L. S., Sperling, R., Teichmann, M., Carrillo, M. C., Cummings, J., & Jack, J. C. R. (2016). Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria. Alzheimer's and Dementia, 12(3), 292–323.
Dwivedi, C., Yadav, R., Tiwari, S., Satapathy, T., & Roy, A. (2014). Role of liposome in novel drug delivery systems. Journal of Drug Delivery and Therapeutics, 4(2), 116–129.
Giannessi, F., Giambelluca, M. A., Grasso, L., Scavuzzo, M. C., & Ruffoli, R. (2008). Curcumin protects Leydig cells of mice from damage induced by chronic alcohol administration. Medical Science Monitor, 14(11), 237–242.
Goel, P., Chakrabarti, S., Goel, K., Bhutani, K., Chopra, T., & Bali, S. (2022). Neuronal cell death mechanisms in Alzheimer's disease: An insight. Frontiers in Molecular Neuroscience, 15, 937133.
Gowda, P., Reddy, P. H., & Kumar, S. (2022). Deregulated mitochondrial microRNAs in Alzheimer’s disease: Focus on synapse and mitochondria. Aging Research Reviews, 73, 101529.
Hagihara, H., Murano, T., Ohira, K., Miwa, M., Nakamura, K., & Miyakawa, T. (2019). Expression of progenitor cell/immature neuron markers does not present definitive evidence for adult neurogenesis. Molecular Brain, 12(1), 108.
Hamid, M. S. S., Hatwar, P. R., Bakal, R. L., & Kohale, N. B. (2024). A comprehensive review on liposomes: As a novel drug delivery system. GSC Biological and Pharmaceutical Sciences, 27(1), 199–210.
Han, C., Yang, Y., Guan, Q., Zhang, X., Shen, H., Sheng, Y., Wang, J., Zhou, X., Li, W., Guo, L., & Jiao, Q. (2020). New mechanism of nerve injury in Alzheimer's disease: β-Amyloid-induced neuronal pyroptosis. Journal of Cellular and Molecular Medicine, 24(14), 8078–8090.
Hatcher, H., Planalp, R., Cho, J., Torti, F. M., & Torti, S. V. (2008). Curcumin: From ancient medicine to current clinical trials. Cellular and Molecular Life Sciences, 65(11), 1631–1652.
Hébert, S. S., Horré, K., Nicolaï, L., Bergmans, B., Papadopoulou, A. S., Delacourte, A., & de Strooper, B. (2009). MicroRNA regulation of Alzheimer’s amyloid precursor protein expression. Neurobiology of Disease, 33(3), 422–428.
Jaruga, E., Salvioli, S., Dobrucki, J., Chrul, S., Bandorowicz-Pikuła, J., Sikora, E., Franceschi, C., Cossarizza, A., & Bartosz, G. (1998). Apoptosis-like, reversible changes in plasmamembrane asymmetry and permeability, and transient modifications in mitochondrial membrane potential induced by curcumin in rat thymocytes. Federation of European Biochemical Societies Letters, 433(3), 287–293.
Jefremov, V., Zilmer, M., Zilmer, K., Bogdanovic, N., & Karelson, E. (2007). Antioxidative effects of plant polyphenols: From protection of G protein signaling to prevention of age-related pathologies. Annals of the New York Academy of Sciences, 1095, 449–457.
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018). Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement, 4, 575–590.
Kot, K., Kot, Y., Kurbanov, R., Andriiash, H., Tigunova, O., Blume, Y., & Shulga, S. (2024). The effect of human PBMCs immobilization on their Аβ42 aggregates-dependent proinflammatory state on a cellular model of Alzheimer’s disease. Frontiers of Neuroscience, 18, 1325287.
Kundu, P., Mohanty, C., & Sahoo, S. (2012). Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy. Acta Biomaterialia, 8(7), 2670–2687.
Kwon, H. S., & Koh, S. H. (2020). Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes. Translational Neurodegeneration, 9, 42.
Lachance, V., Wang, Q., Sweet, E., Choi, I., Cai, C. Z., Zhuang, X. X., Zhang, Y., Jiang, J. L., Blitzer, R. D., Bozdagi-Gunal, O., Zhang, B., Lu, J. H., & Yue, Z. (2019). Autophagy protein NRBF2 has reduced expression in Alzheimer's brains and modulates memory and amyloid-beta homeostasis in mice. Molecular Neurodegeneration, 14(1), 43.
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., Lin, C., Socci, N. D., Hermida, L., Fulci, V., Chiaretti, S., Foà, R., Schliwka, J., Fuchs, U., Novosel, A., Müller, R. U., Schermer, B., Bissels, U., Inman, J., Phan, Q., Chien, M., Weir, D. B., Choksi, R., De Vita, G., Frezzetti, D., Trompeter, H. I., Hornung, V., Teng, G., Hartmann, G., Palkovits, M., Di Lauro, R., Wernet, P., Macino, G., Rogler, C. E., Nagle, J. W., Ju, J., Papavasiliou, F. N., Benzing, T., Lichter, P., Tam, W., Brownstein, M. J., Bosio, A., Borkhardt, A., Russo, J. J., Sander, C., Zavolan, M., & Tuschl, T. (2007). A mammalian microRNA expression atlas based on small RNA library sequencing. Cell, 129(7), 1401–1414.
Li, Y. B., Fu, Q., Guo, M., Du, Y., Chen, Y., & Cheng, Y. (2024). MicroRNAs: Pioneering regulators in Alzheimer's disease pathogenesis, diagnosis, and therapy. Translational Psychiatry, 14(1), 367.
Lin, J., & Shih, C. A. (1994). Inhibitory effect of curcumin on xanthine dehydrogenase/oxidase induced by phorbol-12-myristate-13- acetate in NIH3T3 cells. Carcinogenesis, 15(8), 1717–1721.
Liu, L., Zhang, P., Li, Y., & Yu, G. (2012). Curcumin protects brain from oxidative stress through inducing expression of UCP2 in chronic cerebral hypoperfusion aging-rats. Molecular Neurodegeneration, 7(S1), S10.
Liu, W. L., Lin, H. W., Lin, M. R., Yu, Y., Liu, H. H., Dai, Y. L., Chen, L. W., Jia, W. W., He, X. J., Li, X. L., Zhu, J. F., Xue, X. H., Tao, J., & Chen, L. D. (2022). Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer's disease: A meta-analysis and systematic review. Neural Regeneration Research, 17(11), 2381–2390.
Mishra, H., Chauhan, V., Kumar, K., & Teotia, D. (2018). A comprehensive review on liposomes: A novel drug delivery system. Journal of Drug Delivery and Therapeutics, 8(6), 400–404.
Mutsuga, M., Chambers, J. K., Uchida, K., Tei, M., Makibuchi, T., Mizorogi, T., Takashima, A., & Nakayama, H. (2012). Binding of curcumin to senile plaques and cerebral amyloid angiopathy in the aged brain of various animals and to neurofibrillary tangles in Alzheimer's brain. Journal of Veterinary Medical Science, 74(1), 51–57.
Noorafshan, A., & Ashkani-Esfahani, S. (2012). A review of therapeutic effects of curcumin. Current Pharmaceutical Design, 19(11), 2032–2046.
Oliver, D. M. A., & Reddy, P. H. (2019). Molecular basis of Alzheimer’s disease: Focus on mitochondria. Journal of Alzheimer’s Disease, 72, S95–S116.
Pereira, J. B., Janelidze, S., Ossenkoppele, R., Kvartsberg, H., Brinkmalm, A., Mattsson-Carlgren, N., Stomrud, E., Smith, R., Zetterberg, H., Blennow, K., & Hansson, O. (2021). Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer's disease. Brain, 144(1), 310–324.
Purkayastha, S., Berliner, A., Fernando, S. S., Ranasinghe, B., Ray, I., Tariq, H., & Banerjee, P. (2009). Curcumin blocks brain tumor formation. Brain Research, 1266, 130–138.
Qiu, C., Kivipelto, M., & von Strauss, E. (2009). Epidemiology of Alzheimer's disease: Occurrence, determinants, and strategies toward intervention. Dialogues in Clinical Neuroscience, 11(2), 111–128.
Rathore, S., Mukim, M., Sharma, P., Devi, S., Nagar, J. C., & Khalid, M. (2020). Curcumin: A review for health benefits. International Journal of Research and Review, 7(1), 273–290.
Reitz, C., & Mayeux, R. (2014). Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers. Biochemical Pharmacology, 88(4), 640–651.
Saleem, S. (2021). Apoptosis, autophagy, necrosis and their multi galore crosstalk in neurodegeneration. Neuroscience, 469, 162–174.
Sawant, G. S., Sutar, K. V., & Kanekar, A. S. (2021). Liposome: A novel drug delivery system. International Journal of Research and Review, 8(4), 252–268.
Sercombe, L., Veerati, T., Moheimani, F., Wu, S., Sood, A., & Hua, S. (2015). Advances and challenges of liposome assisted drug delivery. Frontiers in Pharmacology, 6, 286.
Sharma, D., Ali, A. A. E., & Trivedi, L. R. (2018). An updated review on: Liposomes as drug delivery system. PharmaTutor, 6(2), 50–62.
Shulga, S. (2013). Liposomes and nanosomes: Structure, properties, production. Biotechnologia Acta, 6(5), 19–40.
Shulga, S., Andriiash, H., Tigunova, O., Blume, Y., & Priyomov, S. (2025). Creation and application of liposomal form of microRNA for the treatment of neurodenegratative diseases. Cytology ana Genetics, 59, 197–205.
Silvestro, S., Bramanti, P., & Mazzon, E. (2019). Role of miRNAs in Alzheimer’s disease and possible fields of application. International Journal of Molecular Sciences, 20, 3979.
Singh, M., & Singh, N. (2011). Curcumin counteracts the proliferative effect of estradiol and induces apoptosis in cervical cancer cells. Molecular and Cellular Biochemistry, 347(1–2), 1–11.
Sreejayan, R. M. (1997). Nitric oxide scavenging by curcuminoids. Journal of Pharmacy and Pharmacology, 49(1), 105–107.
Tian, M., Wang, L., Yu, G., Liu, B., & Yu, L. (2012). Curcumin promotes cholesterol efflux from brain through LXR/RXR-ABCA1-apoA1 pathway in chronic cerebral hypoperfusion aging-rats. Molecular Neurodegeneration, 7(1), S7.
Tiwari, S.,Talreja, S., & Pandey, S. (2020). A review on use of novel drug delivery systems in herbal medicines. Science and Engineering Journal, 24(8), 190–197.
Tomiyama, T., Matsuyama, S., Iso, H., Umeda, T., Takuma, H., Ohnishi, K., Ishibashi, K., Teraoka, R., Sakama, N., Yamashita, T., Nishitsuji, K., Ito, K., Shimada, H., Lambert, M. P., Klein, W. L., & Mori, H. (2010). A mouse model of amyloid beta oligomers: Their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo. Journal of Neuroscience, 30(14), 4845–4856.
Treiber, T., Treiber, N., & Meister, G. (2019). Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nature Reviews. Molecular Cell Biology, 20, 5–20.
Urošević, M., Nikolić, L., Gajić, I., Nikolić, V., Dinić, A., & Miljković, V. (2022). Curcumin: Biological activities and modern pharmaceutical forms. Antibiotics, 11(2), 135.
Xu, C., Wu, J., Wu, Y., Ren, Z., Yao, Y., Chen, G., Fang, E. F., Noh, J. H., Liu, Y. U., Wei, L., Chen, X., & Sima, J. (2021). TNF-α-dependent neuronal necroptosis regulated in Alzheimer's disease by coordination of RIPK1-p62 complex with autophagic UVRAG. Theranostics, 11(19), 9452–9469.
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024). Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies. Signal Transduction and Targeted Therapy, 9, 211.
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