Alzheimer ve Parkinson hastalıklarında bor içeren bileşiklerin nörokoruyucu etkisi

Yıl 2024, , 42 - 51, 29.03.2024

Barış Bitmez , Beste Balbal

https://doi.org/10.30728/boron.1408368

Öz

Bu derlemede bor içeren bileşiklerin nörodejenerasyon süreci üzerindeki etkileri anlatılmaktadır. Bor içeren bileşikler nöronlar üzerinde çeşitli koruyucu etkiler gösterirler. Son araştırmalar, bor takviyesinin nöronlarda antioksidan savunma mekanizmalarının artmasına yol açtığını, inflamasyonu baskıladığını ve oksidatif hasara karşı iyi bir koruma potansiyeli sergilediğini göstermiştir. Bu doğrultuda yazılan derleme makalesinde, bor içeren bileşiklerin nöro-koruyucu etkilerinin araştırıldığı çalışmalar incelendi ve bor içeren bileşiklerin nörodejeneratif hastalıkların tedavisinde spesifik hedeflere ilaç olarak uygulanmasına ilişkin daha ileri çalışmalara gerek olduğu tespit edildi.

Anahtar Kelimeler

Bor, nörodejenerasyon, Alzheimer Hastalığı, Parkinson Hastalığı, nöroinflamasyon

Neuroprotective Effect of Boron-Containing Compounds on Alzheimer's and Parkinson's Diseases

Öz

This review describes the effects of boron-containing compounds on the neurodegeneration process. Boron-containing compounds show various protective effects on neurons. Recent studies have shown that boron supplementation leads to increased antioxidant defense mechanisms in neurons, suppressing inflammation and exhibiting the potential to protect against oxidative damage. In this review article, studies investigating the neuroprotective effects of boron-containing compounds were examined and it was determined that further studies were needed on the application of boron-containing compounds as drugs to specific targets in the treatment of neurodegenerative diseases.

Anahtar Kelimeler

Boron, neurodegeneration, Alzheimer Disease, Parkinson Disease, neuroinflammation

Kaynakça

• [1] Küçükdoğru, R., Türkez, H., Arslan, M. E., Tozlu, Ö. Ö., Sönmez, E., Mardinoğlu, A., ... & Di Stefano, A. (2020). Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis. Metabolic Brain Disease, 35, 947-957. https://doi.org/10.1007/s11011-020-00559-6.
• [2]. Acaroz, U., Ince, S., Arslan-Acaroz, D., Gurler, Z., Kucukkurt, I., Demirel, H. H., ... & Zhu, K. (2018). The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food and Chemical Toxicology, 118, 745-752. https://doi.org/10.1016/j.fct.2018.06.029.
• [3]. Turkez, H., Yıldırım, S., Sahin, E., Arslan, M. E., Emsen, B., Tozlu, O. O., ... & Mardinoglu, A. (2022). Boron compounds exhibit protective effects against aluminuminduced neurotoxicity and genotoxicity: In vitro and in vivo study. Toxics, 10(8), 428. https://doi.org/10.3390/ toxics10080428.
• [4]. Lu, C. J., Hu, J., Wang, Z., Xie, S., Pan, T., Huang, L., & Li, X. (2018). Discovery of boron-containing compounds as Aβ aggregation inhibitors and antioxidants for the treatment of Alzheimer's disease. MedChemComm, 9(11), 1862-1870. https://doi.org/10.1039/C8MD00315G.
• [5]. Nielsen, F. H. (2014). Update on human health effects of boron. Journal of Trace Elements in Medicine and Biology, 28(4), 383-387. https://doi.org/10.1016/j. jtemb.2014.06.023.
• [6]. Khaliq, H., Juming, Z., & Ke-Mei, P. (2018). The physiological role of boron on health. Biological Trace Element Research, 186, 31-51. https://doi.org/10.1007/ s12011-018-1284-3.
• [7]. Ozdemir, H. S., Yunusoglu, O., Sagmanligil, V., Yasar, S., Colcimen, N., Goceroglu, R., & Catalkaya, E. (2022). Investigation of the pharmacological, behavioral, and biochemical effects of boron in parkinson-indicated rats. Cellular and Molecular Biology, 68(8), 13-21. https://doi. org/10.14715/cmb/2022.68.8.3.
• [8]. Ma, C., Hong, F., & Yang, S. (2022). Amyloidosis in Alzheimer’s disease: Pathogeny, etiology, and related therapeutic directions. Molecules, 27(4), 1210. https:// doi.org/10.3390/molecules27041210.
• [9]. Tahami Monfared, A. A., Byrnes, M. J., White, L. A., & Zhang, Q. (2022). Alzheimer’s disease: Epidemiology and clinical progression. Neurology and Therapy, 11(2), 553-569. https://doi.org/10.1007/s40120-022-00338-8.
• [10]. Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., ... & Vergallo, A. (2021). The amyloid-β pathway in Alzheimer’s disease. Molecular Psychiatry, 26(10), 5481-5503. https://doi.org/10.1038/ s41380-021-01249-0.
• [11]. Calabrò, M., Rinaldi, C., Santoro, G., & Crisafulli, C. (2021). The biological pathways of Alzheimer disease: A review. AIMS Neuroscience, 8(1), 86-132. https://doi. org/10.3934/Neuroscience.2021005.
• [12]. Akkuş, R. Y., Bitmez, B., Gültekin, S. K., Albayrak, İ. G., Özen F., Deveci, Y., ... & Arslan, B. A. (2022). Neuroprotective effect of Hypericum perforatum extract against aluminum-maltolate induced toxicity in SHSY5Y cells. International Journal of Science Letters, 4(2), 277-291. https://doi.org/10.38058/ijsl.1121636.
• [13]. Peng, L., Bestard-Lorigados, I., & Song, W. (2022). The synapse as a treatment avenue for Alzheimer’s Disease. Molecular Psychiatry, 27(7), 2940-2949. https://doi.org/10.1038/s41380-022-01565-z.
• [14]. Šimić, G., Španić, E., Horvat, L. L., & Hof, P. R. (2019). Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease. Progress in Molecular Biology and Translational Science, 168, 99- 145. https://doi.org/10.1016/bs.pmbts.2019.06.003.
• [15]. Yuksel, M., & Tacal, O. (2019). Trafficking and proteolytic processing of amyloid precursor protein and secretases in Alzheimer's disease development: An up-to-date review. European Journal of Pharmacology, 856, 172415. https://doi.org/10.1016/j.ejphar.2019.172415.
• [16]. Chen, G. F., Xu, T. H., Yan, Y., Zhou, Y. R., Jiang, Y., Melcher, K., & Xu, H. E. (2017). Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacologica Sinica, 38(9), 1205-1235. https:// doi.org/10.1038/aps.2017.28.
• [17]. Liu, X., Liu, Y., & Ji, S. (2021). Secretases related to amyloid precursor protein processing. Membranes, 11(12), 983. https://doi.org/10.3390/ membranes11120983.
• [18]. Idda, M. L., Munk, R., Abdelmohsen, K., & Gorospe,M. (2018). Noncoding RNAs in Alzheimer's disease. WIREs RNA, 9(2), e1463. https://doi.org/10.1002/ wrna.1463.
• [19]. Siddappaji, K. K., & Gopal, S. (2021). Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches. AIMS Neuroscience, 8(3), 357-389. https://doi.org/10.3934/Neuroscience.2021020.
• [20]. Bahk, Y. Y., Mohamed, B., & Kim, Y. J. (2013). Biomedical application of phosphoproteomics in neurodegenerative diseases. Journal of Microbiology and Biotechnology, 23(3), 279-288. https://doi. org/10.4014/jmb.1301.01027.
• [21]. Wu, Y., & Eisel, U. L. M. (2023). Microglia-Astrocyte Communication in Alzheimer’s Disease. Journal of Alzheimer's Disease, 95(3), 785-803. https://doi. org/10.3233/JAD-230199.
• [22]. Sharma, K., Pradhan, S., Duffy, L. K., Yeasmin, S., Bhattarai, N., & Schulte, M. K. (2021). Role of receptors in relation to plaques and tangles in Alzheimer’s disease pathology. International Journal of Molecular Sciences, 22(23), 12987. https://doi.org/10.3390/ijms222312987.
• [23]. Kumari, S., Dhapola, R., & Reddy, D. H. (2023). Apoptosis in Alzheimer’s disease: Insight into the signaling pathways and therapeutic avenues. Apoptosis, 1-15. https://doi.org/10.1007/s10495-023-01848-y.
• [24]. Brunello, C. A., Merezhko, M., Uronen, R. L., & Huttunen, H. J. (2020). Mechanisms of secretion and spreading of pathological tau protein. Cellular and Molecular Life Sciences, 77, 1721-1744. https://doi. org/10.1007/s00018-019-03349-1.
• [25]. Narayanan, S. E., Rehuman, N. A., Harilal, S., Vincent, A., Rajamma, R. G., Behl, T., ... & Mathew, B. (2020). Molecular mechanism of zinc neurotoxicity in Alzheimer’s disease. Environmental Science and Pollution Research, 27, 43542-43552. https://doi. org/10.1007/s11356-020-10477-w.
• [26]. Rawat, P., Sehar, U., Bisht, J., Selman, A., Culberson, J., & Reddy, P. H. (2022). Phosphorylated tau in Alzheimer’s disease and other tauopathies. International Journal of Molecular Sciences, 23(21), 12841. https:// doi.org/10.3390/ijms232112841.
• [27]. Muralidar, S., Ambi, S. V., Sekaran, S., Thirumalai, D., & Palaniappan, B. (2020). Role of tau protein in Alzheimer's disease: The prime pathological player. International Journal of Biological Macromolecules, 163, 1599-1617. https://doi.org/10.1016/j.ijbiomac.2020.07.327.
• [28]. Al Mamun, A., Uddin, M. S., Mathew, B., & Ashraf, G. M. (2020). Toxic tau: Structural origins of tau aggregation in Alzheimer's disease. Neural Regeneration Research, 15(8), 1417. https://doi.org/10.4103/1673-5374.274329.
• [29]. Mineur, Y. S., & Picciotto, M. R. (2021). The role of acetylcholine in negative encoding bias: Too much of a good thing?. European Journal of Neuroscience, 53(1), 114-125. https://doi.org/10.1111/ejn.14641.
• [30]. Pepeu, G., & Giovannini, M. G. (2017). The fate of the brain cholinergic neurons in neurodegenerative diseases. Brain Research, 1670, 173-184. https://doi. org/10.1016/j.brainres.2017.06.023.
• [31]. Majdi, A., Sadigh-Eteghad, S., Rahigh Aghsan, S., Farajdokht, F., Vatandoust, S. M., Namvaran, A., & Mahmoudi, J. (2020). Amyloid-β, tau, and the cholinergic system in Alzheimer’s disease: Seeking direction in a tangle of clues. Reviews in the Neurosciences, 31(4), 391-413. https://doi.org/10.1515/revneuro-2019-0089.
• [32]. Chen, Z. R., Huang, J. B., Yang, S. L., & Hong, F. F. (2022). Role of cholinergic signaling in Alzheimer’s disease. Molecules, 27(6), 1816. https://doi. org/10.3390/molecules27061816.
• [33]. Liu, Y., Nguyen, M., Robert, A., & Meunier, B. (2019). Metal ions in Alzheimer’s disease: A key role or not?. Accounts of Chemical Research, 52(7), 2026-2035. https://doi.org/10.1002/brb3.252.
• [34]. Li, Z., Liu, Y., Wei, R., Yong, V. W., & Xue, M. (2022). The important role of zinc in neurological diseases. Biomolecules, 13(1), 28. https://doi.org/10.3390/ biom13010028.
• [35]. Huat, T. J., Camats-Perna, J., Newcombe, E. A., Valmas, N., Kitazawa, M., & Medeiros, R. (2019). Metal toxicity links to Alzheimer's disease and neuroinflammation. Journal of Molecular Biology, 431(9), 1843-1868. https://doi.org/10.1016/j.jmb.2019.01.018.
• [36]. Balachandran, R. C., Mukhopadhyay, S., McBride, D., Veevers, J., Harrison, F. E., Aschner, M., ... & Bowman, A. B. (2020). Brain manganese and the balance between essential roles and neurotoxicity. Journal of Biological Chemistry, 295(19), 6312-6329. https://doi. org/10.1074/jbc.REV119.009453.
• [37]. Martins Jr, A. C., Gubert, P., Villas Boas, G. R., Meirelles Paes, M., Santamaría, A., Lee, E., ... & Aschner, M. (2020). Manganese-induced neurodegenerative diseases and possible therapeutic approaches. Expert Review of Neurotherapeutics, 20(11), 1109-1121. https://doi.org/10.1080/14737175.2020.1807330.
• [38]. Mezzaroba, L., Alfieri, D. F., Simão, A. N. C., & Reiche, E. M. V. (2019). The role of zinc, copper, manganese and iron in neurodegenerative diseases. Neurotoxicology, 74, 230-241. https://doi.org/10.1016/j. neuro.2019.07.007.
• [39]. Viktorinova, A., & Durfinova, M. (2021). Mini- Review: Is iron-mediated cell death (ferroptosis) an identical factor contributing to the pathogenesis of some neurodegenerative diseases?. Neuroscience Letters, 745, 135627. https://doi.org/10.1016/j. neulet.2021.135627.
• [40]. Kajarabille, N., & Latunde-Dada, G. O. (2019). Programmed cell-death by ferroptosis: Antioxidants as mitigators. International Journal of Molecular Sciences, 20(19), 4968. https://doi.org/10.3390/ijms20194968.
• [41]. Gong, N. J., Dibb, R., Bulk, M., van der Weerd, L., & Liu, C. (2019). Imaging beta amyloid aggregation and iron accumulation in Alzheimer's disease using quantitative susceptibility mapping MRI. Neuroimage, 191, 176-185. https://doi.org/10.1016/j.neuroimage.2019.02.019.
• [42]. Eriksen, J. L., Wszolek, Z., & Petrucelli, L. (2005). Molecular pathogenesis of Parkinson disease. Archives of Neurology, 62(3), 353-357. https://doi.org/10.1001/ archneur.62.3.353.
• [43]. Bitmez, B., Gultekin, S. K., Albayrak, I. G., Deveci, Y., Sicak, Y., Akalin, E., ... & Arslan, B. A. (2023). Effects of Hypericum perforatum extract on 6-hydroxydopamine neurotoxicity in differentiated SH-SY5Y cells. Egyptian Pharmaceutical Journal, 22(2), 188-191. https://doi. org/10.4103/epj.epj_180_22.
• [44]. Lee, A., & Gilbert, R. M. (2016). Epidemiology of Parkinson disease. Neurologic Clinics, 34(4), 955-965. https://doi.org/10.1016/j.ncl.2016.06.012.
• [45]. Durmus, H., Gokalp, M. A., & Hanagasi, H. A. (2015). Prevalence of Parkinson’s disease in Baskale, Turkey: A population based study. Neurological sciences, 36(3), 411-413. https://doi.org/10.1007/s10072-014-1988-x.
• [46]. Olgun, H., Zayimoğlu, E., & Cankaya, S. (2018). Incidence of sarcopenia and dynapenia according to stage in patients with idiopathic Parkinson’s disease. Neurological Sciences, 39(8), 1415-1421. https://doi. org/10.1007/s10072-018-3439-6.
• [47]. Siddique, Y. H. (2022). Drosophila: A Model to study the pathogenesis of Parkinson’s disease. CNS & Neurological Disorders-Drug Targets, 21(3), 259-277. https://doi.org/10.2174/1871527320666210809120621.
• [48]. Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., ... & Lang, A. E. (2017). Parkinson disease. Nature Reviews Disease Primers, 3(1), 1-21. https://doi.org/10.1038/nrdp.2017.13.
• [49]. Picca, A., Calvani, R., Coelho-Junior, H. J., Landi, F., Bernabei, R., & Marzetti, E. (2020). Mitochondrial dysfunction, oxidative stress, and neuroinflammation: Intertwined roads to neurodegeneration. Antioxidants, 9(8), 647. https://doi.org/10.3390/antiox9080647.
• [50]. Bose, A., & Beal, M. F. (2016). Mitochondrial dysfunction in Parkinson's disease. Journal of Neurochemistry, 139, 216-231. https://doi.org/10.1111/jnc.13731.
• [51]. Kim, T. Y., Leem, E., Lee, J. M., & Kim, S. R. (2020). Control of reactive oxygen species for the prevention of parkinson’s disease: The possible application of flavonoids. Antioxidants, 9(7), 583. https://doi. org/10.3390/antiox9070583.
• [52]. Sheridan, C., Delivani, P., Cullen, S. P., & Martin, S. J. (2008). Bax- or Bak-induced mitochondrial fission can be uncoupled from cytochrome C release. Molecular Cell, 31, 570-585. https://doi.org/10.1016/j. molcel.2008.08.002.
• [53]. Villalpando-Rodriguez, G. E., & Gibson, S. B. (2021). Reactive oxygen species (ROS) regulates different types of cell death by acting as a rheostat. Oxidative Medicine and Cellular Longevity, 2021, 9912436. https://doi.org/10.1155/2021/9912436.
• [54]. Erekat, N. S. (2022). Apoptosis and its therapeutic implications in neurodegenerative diseases. Clinical Anatomy, 35(1), 65-78. https://doi.org/10.1002/ ca.23792.
• [55]. Dionísio, P. A., Amaral, J. D., & Rodrigues, C. M. P. (2021). Oxidative stress and regulated cell death in Parkinson’s disease. Ageing Research Reviews, 67, 101263. https://doi.org/10.1016/j.arr.2021.101263.
• [56]. Kitagishi, Y., Nakano, N., Ogino, M., Ichimura, M., Minami, A., & Matsuda, S. (2017). PINK1 signaling in mitochondrial homeostasis and in aging. International Journal of Molecular Medicine, 39(1), 3-8. https://doi. org/10.3892/ijmm.2016.2827.
• [57]. Dawson, T. M., & Dawson, V. L. (2018). Excitotoxic programmed cell death involves caspase-independent mechanisms. Acute Neuronal Injury (pp. 3-17). Springer, Cham. https://doi.org/10.1007/978-3-319-77495-4_1.
• [58]. Behl, T., Kumar, S., Althafar, Z. M., Sehgal, A., Singh, S., Sharma, N., ... & Bungau, S. (2022). Exploring the role of ubiquitin–proteasome system in Parkinson's disease. Molecular Neurobiology, 59(7), 4257-4273. https://doi.org/10.1007/s12035-022-02851-1.
• [59]. Moon, H. E., & Paek, S. H. (2015). Mitochondrial dysfunction in Parkinson's disease. Experimental Neurobiology, 24(2), 103. https://doi.org/10.5607/ en.2015.24.2.103
• [60]. More, S. V., Kumar, H., Kim, I. S., Song, S. Y., & Choi, D. K. (2013). Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson’s disease. Mediators of Inflammation, 2013, 952375. https://doi.org/10.1155/2013/952375.
• [61]. Weiss, F., Labrador-Garrido, A., Dzamko, N., & Halliday, G. (2022). Immune responses in the Parkinson's disease brain. Neurobiology of Disease, 168, 105700. https://doi.org/10.1016/j.nbd.2022.105700.
• [62]. Isik, S., Yeman Kiyak, B., Akbayir, R., Seyhali, R., & Arpaci, T. (2023). Microglia mediated neuroinflammation in Parkinson’s disease. Cells, 12(7), 1012. https://doi. org/10.3390/cells12071012.
• [63]. Simon, D. K., Tanner, C. M., & Brundin, P. (2020). Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clinics in Geriatric Medicine, 36(1), 1-12. https://doi.org/10.1016/j.cger.2019.08.002.
• [64]. Deng, H., Wang, P., & Jankovic, J. (2018). The genetics of Parkinson disease. Ageing Research Reviews, 42, 72-85. https://doi.org/10.1016/j.arr.2017.12.007.
• [65]. Turkez, H., Yıldırım, S., Sahin, E., Arslan, M. E., Emsen, B., Tozlu, O. O., ... & Mardinoglu, A. (2022). Boron compounds exhibit protective effects against aluminum-induced neurotoxicity and genotoxicity: In vitro and in vivo study. Toxics, 10(8), 428. https://doi. org/10.3390/toxics10080428.
• [66]. Kar, F, Hacıoğlu, C., Özkoç, M., Üstünışık, N., Bütün, A., Sema, U., & Kanbak, G. (2018). The new perspective neuroprotective effect of boric acid against ethanolinduced oxidative damage on synaptosome. Journal of Applied Biological Sciences, 12(2), 28-33.
• [67]. Ataizi, Z. S., Ozkoc, M., Kanbak, G., Karimkhani, H., Donmez, D. B., Ustunisik, N., & Ozturk, B. (2021). Evaluation of the neuroprotective role of boric acid in preventing traumatic brain injury-mediated oxidative stress. Turkish Neurosurgery, 31(4), 25692-18. https:// doi.org/10.5137/1019-5149.JTN.25692-18.5.
• [68]. İlhan, A. O., Can, B., Kar, F., Gündoğdu, A. Ç., Söğüt, İ., & Kanbak, G. (2023). An investigation into the protective effects of various doses of boric acid on liver, kidney, and brain tissue damage caused by high levelsof acute alcohol consumption. Biological Trace Element Research, 201, 5346–5357. https://doi.org/10.1007/ s12011-023-03699-9.
• [69]. Alak, G., Ucar, A., Yeltekin, A. Ç., Çomaklı, S., Parlak, V., Taş, I. H., ... & Türkez, H. (2018). Neuroprotective effects of dietary borax in the brain tissue of rainbow trout (Oncorhynchus mykiss) exposed to copper-induced toxicity. Fish Physiology and Biochemistry, 44, 1409- 1420. https://doi.org/10.1007/s10695-018-0530-0.
• [70]. Coban, F. K., Ince, S., Kucukkurt, I., Demirel, H. H., & Hazman, O. (2015). Boron attenuates malathioninduced oxidative stress and acetylcholinesterase inhibition in rats. Drug and Chemical Toxicology, 38(4), 391-399. https://doi.org/10.3109/01480545.2014.9741 09.
• [71]. Acaroz, U., Ince, S., Arslan-Acaroz, D., Gurler, Z., Demirel, H. H., Kucukkurt, I., ... & Zhu, K. (2019). Bisphenol-A induced oxidative stress, inflammatory gene expression, and metabolic and histopathological changes in male Wistar albino rats: Protective role of boron. Toxicology Research, 8(2), 262-269. https://doi. org/10.1039/c8tx00312b.
• [72]. Ince, S., Kucukkurt, I., Acaroz, U., Arslan-Acaroz, D., & Varol, N. (2019). Boron ameliorates arsenicinduced DNA damage, proinflammatory cytokine gene expressions, oxidant/antioxidant status, and biochemical parameters in rats. Journal of Biochemical and Molecular Toxicology, 33(2), e22252. https://doi. org/10.1002/jbt.22252.
• [73]. Sahin, N., Akdemir, F., Orhan, C., Aslan, A., Agca, C. A., Gencoglu, H., ... & Sahin, K. (2012). A novel nutritional supplement containing chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron activates the antioxidant pathway Nrf2/HO-1 and protects the brain against oxidative stress in high-fatfed rats. Nutritional Neuroscience, 15(5), 42-47. https:// doi.org/10.1179/1476830512Y.0000000018.
• [74]. Orhan, C., Şahin, N., Tuzcu, Z., Komorowski, J. R., & Şahin, K. (2017). Combined oral supplementation of chromium picolinate, docosahexaenoic acid, and boron enhances neuroprotection in rats fed a high-fat diet. Turkish Journal of Medical Sciences, 47(5), 1616-1625. https://doi.org/ 10.3906/sag-1701-54.
• [75]. Hacioglu, C., Kar, F., Kar, E., Kara, Y., & Kanbak, G. (2021). Effects of curcumin and boric acid against neurodegenerative damage induced by amyloid beta (1-42). Biological Trace Element Research, 199, 3793- 3800. https://doi.org/10.1007/s12011-020-02511-2.
• [76]. Özdemir, Ç., Arslan, M., Küçük, A., Yığman, Z., & Dursun, A. D. (2023). Therapeutic efficacy of boric acid treatment on brain tissue and cognitive functions in rats with experimental Alzheimer’s disease. Drug Design, Development and Therapy, 1453-1462. https://doi. org/10.2147/DDDT.S405963.
• [77]. Yildirim, C., Yar Saglam, A. S., Guney, S., Turan, B., Ebegil, M., Coskun Cevher, S., & Balabanli, B. (2023). Investigation covering the effect of boron plus taurine application on protein carbonyl and advanced oxidation protein products levels in experimental Alzheimer model. Biological Trace Element Research, 201(4), 1905-1912. https://doi.org/ 10.1007/s12011-022-03293-5.
• [78]. Hu, W. Y., He, Z. Y., Yang, L. J., Zhang, M., Xing, D., & Xiao, Z. C. (2015). The Ca 2+ channel inhibitor 2-APB reverses β-amyloid-induced LTP deficit in hippocampus by blocking Bax and caspase-3 hyperactivation. British Journal of Pharmacology, 172(9), 2273-2285. https:// doi.org/10.1111/bph.13048.
• [79]. Abad-García, A., Ocampo-Néstor, A. L., Das, B. C., Farfán-García, E. D., Bello, M., Trujillo-Ferrara, J. G., & Soriano-Ursúa, M. A. (2022). Interactions of a boron-containing levodopa derivative on D 2 dopamine receptor and its effects in a Parkinson disease model. JBIC Journal of Biological Inorganic Chemistry, 1-11. https://doi.org/10.1007/s00775-021-01915-2.
• [80]. Yavuz, E., Çevik, G., Çevreli, B., & Kaşıkçı, E. S. (2023). Effect of boric acid and quercetin combination on oxidative stress/cognitive function in parkinson model. Journal of Boron, 8(3), 85-91. https://doi.org/10.30728/ boron.1215949.
• [81]. Üstündağ, F. D., Ünal, İ., Üstündağ, Ü. V., Cansız, D., Beler, M., Karagöz, A., ... & Emekli-Alturfan, E. (2022). 3-Pyridinylboronic acid ameliorates rotenone-induced oxidative stress through Nrf2 target genes in zebrafish embryos. Neurochemical Research, 47(6), 1553-1564. https://doi.org/10.1007/s11064-022-03548-6.
• [82]. Vaidya, B., Kaur, H., Thapak, P., Sharma, S. S., & Singh, J. N. (2022). Pharmacological modulation of TRPM2 channels via PARP pathway leads to neuroprotection in MPTP-induced Parkinson’s disease in Sprague dawley rats. Molecular Neurobiology, 59(3), 1528-1542. https:// doi.org/10.1007/s12035-021-02711-4.
• [83]. Smida, K., Albedah, M. A., Rashid, R. F., & Al-Qawasmi, A. R. (2023). Molecular dynamics method for targeting α-synuclein aggregation induced Parkinson's disease using boron nitride nanostructures. Engineering Analysis with Boundary Elements, 146, 89-95. https:// doi.org/10.1016/j.enganabound.2022.10.016.
• [84]. Barrón-González, M., Montes-Aparicio, A. V., Cuevas- Galindo, M. E., Orozco-Suárez, S., Barrientos, R., Alatorre, A., ... & Soriano-Ursúa, M. A. (2023). Boroncontaining compounds on neurons: Actions and potential applications for treating neurodegenerative diseases. Journal of Inorganic Biochemistry, 238, 112027. https:// doi.org/10.1016/j.jinorgbio.2022.112027.