r-n-jРоссийский неврологический журналRussian neurological journal2658-79472686-7192МИА10.30629/2658-7947-2023-28-6-19-33r-n-j-500Research ArticleОБЗОРЫREVIEWSИзучение возможностей лечения болезни Альцгеймера: текущий статус и перспективы на будущееExploring avenues for Alzheimer’s drugs: current status and future outlookhttps://orcid.org/0000-0002-6407-6739РатхиК.RathiK.

Пимпри, Пуна

Dr. Karishma M. Rathi

Pimpri, Pune

karishma.rathi@dypvp.edu.inhttps://orcid.org/0000-0003-1614-9742ВавхалеР.WavhaleR.

Пимпри, Пуна

Pimpri, Pune

ravindra.wavhale@dypvp.edu.inhttps://orcid.org/0000-0003-3837-7471УндалеВ.Undale V.V.

Пимпри, Пуна

Pimpri, Pune

vaishali.undale@dypvp.edu.inhttps://orcid.org/0000-0002-6407-6739БхолеР.BholeR.

Пимпри, Пуна

Pimpri, Pune

ritesh.bhole@dypvp.edu.inhttps://orcid.org/0000-0003-3280-4508ДерангеС.DherangeS.

Пимпри, Пуна

Pimpri, Pune

snehaldherange2018@gmail.comИнститут фармацевтических наук и исследований Д.Ю. ПатилаИндияDr. D.Y. Patil Institute of Pharmaceutical Sciences and ResearchIndiaИнститут фармацевтических наук и исследований Д.Ю. Патила; Стоматологический колледж и больница Д.Ю. Патила, доктор Д.Ю. Патил ВидьяпитИндияDr. D.Y. Patil Institute of Pharmaceutical Sciences and Research; Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil VidyapeethIndia2023080120242861933Copyright © Ратхи К., Вавхале Р., Ундале В., Бхоле Р., Деранге С., 20242024Ратхи К., Вавхале Р., Ундале В., Бхоле Р., Деранге С.Rathi K., Wavhale R., Undale V. V., Bhole R., Dherange S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.r-n-j.com/jour/article/view/500

Болезнь Альцгеймера (БА) — это прогрессирующее неврологическое заболевание, которое вызывает нарушения памяти и другие когнитивные расстройства у пожилых людей. Существует широкий спектр нарушений, включая таупатии, которые отвечают за прогрессирующий нейрональный дегенеративный процесс. При том что исследователи, занимающиеся поиском лекарств, и фармацевтические компании активно работают над разработкой новых препаратов для лечения БА, установление доказательств их безопасности и эффективности вызывает значительные сложности. В обзоре обсуждается патогенез БА с фокусом внимания на молекулярных мишенях, их физиологическом и патофизиологическом значении, терапевтических подходах и их перспективах. Представлена информация о новых многообещающих мишенях для лекарственного воздействия и ведущих базах данных, которые могут помочь выбрать подходящие мишени и разработать новые молекулы для лечения БА.

Alzheimer’s disease (AD) is a progressive neurological disease that causes cognitive impairment in old aged persons. It is the cause of a wide spectrum of neurodegenerative disturbances including tauopathies, which are responsible for progressive neuronal degeneration and impaired cognitive functions. Although drug discovery researchers and pharmaceutical companies are meticulously working to develop novel drugs for AD, establishing their safety and efficacy proofs are major challenges for them. In this review, we have discussed about AD and its causes mainly focusing on molecular targets with their physiological and pathophysiological roles, therapeutic approaches, and their future perspectives. We have compiled the information about novel and promising drug targets and lead data bases that will help to select appropriate target and design novel drug molecules for the treatment of Alzheimer.

болезнь Альцгеймеранейродегенеративное заболеваниеантиальцгеймеровские мишениантиальцгеймеровские препаратыAlzheimer’s diseaseneurodegenerative disorderanti-Alzheimer drug targetsanti-Alzheimer drugsReferencesHaque R.U., Levey A.I. Alzheimer’s disease: A clinical perspective and future nonhuman primate research opportunities. Proceedings of the National Academy of Sciences. 2019;116(52):26224–9.Haque R.U., Levey A.I. Alzheimer’s disease: A clinical perspective and future nonhuman primate research opportunities. Proceedings of the National Academy of Sciences. 2019;116(52):26224–9.Mendiola-Precoma J., Berumen L.C., Padilla K., Garcia-Alcocer G. Therapies for prevention and treatment of Alzheimer’s disease. BioMed research international. 2016;2016:2589276. doi: 10.1155/2016/2589276Mendiola-Precoma J., Berumen L.C., Padilla K., Garcia-Alcocer G. Therapies for prevention and treatment of Alzheimer’s disease. BioMed research international. 2016;2016:2589276. doi: 10.1155/2016/2589276Kumar A., Singh A. A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacological reports. 2015;67(2):195–203.Kumar A., Singh A. A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacological reports. 2015;67(2):195–203.Silva M.V., Loures C.D., Alves L.C., de Souza L.C., Borges K.B., Carvalho M.D. Alzheimer’s disease: risk factors and potentially protective measures. Journal of biomedical science. 2019;26(1):1–1.Silva M.V., Loures C.D., Alves L.C., de Souza L.C., Borges K.B., Carvalho M.D. Alzheimer’s disease: risk factors and potentially protective measures. Journal of biomedical science. 2019;26(1):1–1.Yiannopoulou K.G., Papageorgiou S.G. Current and future treatments for Alzheimer’s disease. Therapeutic advances in neurological disorders. 2013;6(1):19–33.Yiannopoulou K.G., Papageorgiou S.G. Current and future treatments for Alzheimer’s disease. Therapeutic advances in neurological disorders. 2013;6(1):19–33.DeTure M.A., Dickson D.W. The neuropathological diagnosis of Alzheimer’s disease. Molecular neurodegeneration. 2019;14(1):1–8.DeTure M.A., Dickson D.W. The neuropathological diagnosis of Alzheimer’s disease. Molecular neurodegeneration. 2019;14(1):1–8.Thakur A.K., Kamboj P., Goswami K., Ahuja K. Pathophysiology and management of Alzheimer’s disease: An overview. J. Anal. Pharm. Res. 2018;7(1).Thakur A.K., Kamboj P., Goswami K., Ahuja K. Pathophysiology and management of Alzheimer’s disease: An overview. J. Anal. Pharm. Res. 2018;7(1).Tiwari S., Atluri V., Kaushik A., Yndart A., Nair M. Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. International journal of nanomedicine. 2019;14:5541.Tiwari S., Atluri V., Kaushik A., Yndart A., Nair M. Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. International journal of nanomedicine. 2019;14:5541.Fan L., Mao C., Hu X., Zhang S., Yang Z., Hu Z. et al. New insights into the pathogenesis of Alzheimer’s disease. Frontiers in neurology. 2020;10:1312. doi: 10.3389/fneur.2019.01312Fan L., Mao C., Hu X., Zhang S., Yang Z., Hu Z. et al. New insights into the pathogenesis of Alzheimer’s disease. Frontiers in neurology. 2020;10:1312. doi: 10.3389/fneur.2019.01312Rasool M., Malik A., Qureshi M.S., Manan A., Pushparaj P.N., Asif M. et al. Recent updates in the treatment of neurodegenerative disorders using natural compounds. Evidence-Based Complementary and Alternative Medicine. 2014;2014:979730. doi: 10.1155/2014/979730Rasool M., Malik A., Qureshi M.S., Manan A., Pushparaj P.N., Asif M. et al. Recent updates in the treatment of neurodegenerative disorders using natural compounds. Evidence-Based Complementary and Alternative Medicine. 2014;2014:979730. doi: 10.1155/2014/979730Corbett A., Pickett J., Burns A., Corcoran J., Dunnett S.B., Edison P. et al. Drug repositioning for Alzheimer’s disease. Nature Reviews Drug Discovery. 2012;11(11):833–46.Corbett A., Pickett J., Burns A., Corcoran J., Dunnett S.B., Edison P. et al. Drug repositioning for Alzheimer’s disease. Nature Reviews Drug Discovery. 2012;11(11):833–46.Kumar N., Gahlawat A., Kumar R.N., Singh Y.P., Modi G., Garg P. Drug repurposing for Alzheimer’s disease: in silico and in vitro investigation of FDA-approved drugs as acetylcholinesterase inhibitors. Journal of Biomolecular Structure and Dynamics. 2020:1–5. doi:10.1080/07391102.2020.1844054Kumar N., Gahlawat A., Kumar R.N., Singh Y.P., Modi G., Garg P. Drug repurposing for Alzheimer’s disease: in silico and in vitro investigation of FDA-approved drugs as acetylcholinesterase inhibitors. Journal of Biomolecular Structure and Dynamics. 2020:1–5. doi:10.1080/07391102.2020.1844054Agatonovic-Kustrin S., Kettle C., Morton D.W. A molecular approach in drug development for Alzheimer’s disease. Biomedicine & Pharmacotherapy. 2018;106:553–65.Agatonovic-Kustrin S., Kettle C., Morton D.W. A molecular approach in drug development for Alzheimer’s disease. Biomedicine & Pharmacotherapy. 2018;106:553–65.Goedert M., Spillantini M.G. A century of Alzheimer’s disease. Science. 2006;314(5800):777–81.Goedert M., Spillantini M.G. A century of Alzheimer’s disease. Science. 2006;314(5800):777–81.Crous-Bou M., Minguillón C., Gramunt N., Molinuevo J.L. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimer’s research & therapy. 2017;9(1):1–9.Crous-Bou M., Minguillón C., Gramunt N., Molinuevo J.L. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimer’s research & therapy. 2017;9(1):1–9.Mendiola-Precoma J., Berumen L.C., Padilla K., Garcia-Alcocer G. Therapies for prevention and treatment of Alzheimer’s disease. BioMed research international. 2016;(3):1–17. DOI: 10.1155/2016/2589276Mendiola-Precoma J., Berumen L.C., Padilla K., Garcia-Alcocer G. Therapies for prevention and treatment of Alzheimer’s disease. BioMed research international. 2016;(3):1–17. DOI: 10.1155/2016/2589276Mehta M., Adem A., Sabbagh M. New acetylcholinesterase inhibitors for Alzheimer’s disease. International Journal of Alzheimer’s disease. 2012;2012:728983. doi: 10.1155/2012/728983Mehta M., Adem A., Sabbagh M. New acetylcholinesterase inhibitors for Alzheimer’s disease. International Journal of Alzheimer’s disease. 2012;2012:728983. doi: 10.1155/2012/728983Kumar A., Nisha C.M., Silakari C., Sharma I., Anusha K., Gupta N. et al. Current and novel therapeutic molecules and targets in Alzheimer’s disease. Journal of the Formosan Medical Association. 2016;115(1):3–10.Kumar A., Nisha C.M., Silakari C., Sharma I., Anusha K., Gupta N. et al. Current and novel therapeutic molecules and targets in Alzheimer’s disease. Journal of the Formosan Medical Association. 2016;115(1):3–10.Sharma K. Cholinesterase inhibitors as Alzheimer’s therapeutics. Molecular medicine reports. 2019;20(2):1479–87.Sharma K. Cholinesterase inhibitors as Alzheimer’s therapeutics. Molecular medicine reports. 2019;20(2):1479–87.Talesa V.N. Acetylcholinesterase in Alzheimer’s disease. Mechanisms of ageing and development. 2001;122(16):1961–9.Talesa V.N. Acetylcholinesterase in Alzheimer’s disease. Mechanisms of ageing and development. 2001;122(16):1961–9.Pepeu G., Giovannini M.G. Cholinesterase inhibitors and beyond. Current Alzheimer Research. 2009;6(2):86–96.Pepeu G., Giovannini M.G. Cholinesterase inhibitors and beyond. Current Alzheimer Research. 2009;6(2):86–96.Doraiswamy P.M. The role of the N-methyl-D-aspartate receptor in Alzheimer’s disease: therapeutic potential. Current neurology and neuroscience reports. 2003;3(5):373–8.Doraiswamy P.M. The role of the N-methyl-D-aspartate receptor in Alzheimer’s disease: therapeutic potential. Current neurology and neuroscience reports. 2003;3(5):373–8.Kocahan S., Doğan Z. Mechanisms of Alzheimer’s disease pathogenesis and prevention: the brain, neural pathology, N-methyl-D-aspartate receptors, tau protein and other risk factors. Clinical Psychopharmacology and Neuroscience. 2017;15(1):1.Kocahan S., Doğan Z. Mechanisms of Alzheimer’s disease pathogenesis and prevention: the brain, neural pathology, N-methyl-D-aspartate receptors, tau protein and other risk factors. Clinical Psychopharmacology and Neuroscience. 2017;15(1):1.Malinow R. New developments on the role of NMDA receptors in Alzheimer’s disease. Current opinion in neurobiology. 2012;22(3):559–63.Malinow R. New developments on the role of NMDA receptors in Alzheimer’s disease. Current opinion in neurobiology. 2012;22(3):559–63.Doraiswamy P.M. The role of the N-methyl-D-aspartate receptor in Alzheimer’s disease: therapeutic potential. Current neurology and neuroscience reports. 2003;3(5):373–8.Doraiswamy P.M. The role of the N-methyl-D-aspartate receptor in Alzheimer’s disease: therapeutic potential. Current neurology and neuroscience reports. 2003;3(5):373–8.Olivares D., Deshpande V., Shi Y., Lahiri D., Greig N., Rogers J., Huang X. N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer’s disease, vascular dementia and Parkinson’s disease. Current Alzheimer Research. 2012;9(6):746–58.Olivares D., Deshpande V., Shi Y., Lahiri D., Greig N., Rogers J., Huang X. N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer’s disease, vascular dementia and Parkinson’s disease. Current Alzheimer Research. 2012;9(6):746–58.Kumar A., Nisha C.M., Silakari C., Sharma I., Anusha K., Gupta N. et al. Current and novel therapeutic molecules and targets in Alzheimer’s disease. Journal of the Formosan Medical Association. 2016;115(1):3–10.Kumar A., Nisha C.M., Silakari C., Sharma I., Anusha K., Gupta N. et al. Current and novel therapeutic molecules and targets in Alzheimer’s disease. Journal of the Formosan Medical Association. 2016;115(1):3–10.Geerts H., Grossberg G.T. Pharmacology of acetylcholinesterase inhibitors and N‐methyl‐D‐aspartate receptors for combination therapy in the treatment of Alzheimer’s disease. The Journal of Clinical Pharmacology. 2006;46(S1):8S–16S.Geerts H., Grossberg G.T. Pharmacology of acetylcholinesterase inhibitors and N‐methyl‐D‐aspartate receptors for combination therapy in the treatment of Alzheimer’s disease. The Journal of Clinical Pharmacology. 2006;46(S1):8S–16S.Muralidar S., Ambi S.V., Sekaran S., Thirumalai D., Palaniappan B. Role of tau protein in Alzheimer’s disease: The prime pathological player. International journal of biological macromolecules. 2020;163:1599–617.Muralidar S., Ambi S.V., Sekaran S., Thirumalai D., Palaniappan B. Role of tau protein in Alzheimer’s disease: The prime pathological player. International journal of biological macromolecules. 2020;163:1599–617.Johnson G.V., Hartigan J.A. Tau protein in normal and Alzheimer’s disease brain: an update. Journal of Alzheimer’s disease. 1999;1(4–5):329–51.Johnson G.V., Hartigan J.A. Tau protein in normal and Alzheimer’s disease brain: an update. Journal of Alzheimer’s disease. 1999;1(4–5):329–51.Pluta R., Ułamek-Kozioł M. Tau protein-targeted therapies in Alzheimer’s disease: current state and future perspectives. Exon Publications. 2020;Dec 19:69–82.Pluta R., Ułamek-Kozioł M. Tau protein-targeted therapies in Alzheimer’s disease: current state and future perspectives. Exon Publications. 2020;Dec 19:69–82.Bulic B., Pickhardt M., Mandelkow E.M., Mandelkow E. Tau protein and tau aggregation inhibitors. Neuropharmacology. 2010;59(4–5):276–89.Bulic B., Pickhardt M., Mandelkow E.M., Mandelkow E. Tau protein and tau aggregation inhibitors. Neuropharmacology. 2010;59(4–5):276–89.Thomas T. Monoamine oxidase-B inhibitors in the treatment of Alzheimers disease. Neurobiology of aging. 2000;21(2):343–8.Thomas T. Monoamine oxidase-B inhibitors in the treatment of Alzheimers disease. Neurobiology of aging. 2000;21(2):343–8.Riederer P., Danielczyk W., Grünblatt E. Monoamine oxidase-B inhibition in Alzheimer’s disease. Neurotoxicology. 2004;25(1–2):271–7.Riederer P., Danielczyk W., Grünblatt E. Monoamine oxidase-B inhibition in Alzheimer’s disease. Neurotoxicology. 2004;25(1–2):271–7.Mi Z., Gan B., Yu S., Guo J., Zhang C., Jiang X. et al. Dual-target anti-Alzheimer’s disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity. Journal of enzyme inhibition and medicinal chemistry. 2019;34(1):1489–97.Mi Z., Gan B., Yu S., Guo J., Zhang C., Jiang X. et al. Dual-target anti-Alzheimer’s disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity. Journal of enzyme inhibition and medicinal chemistry. 2019;34(1):1489–97.Youdim M.B., Fridkin M., Zheng H. Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. Mechanisms of ageing and development. 2005;126(2):317–26.Youdim M.B., Fridkin M., Zheng H. Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. Mechanisms of ageing and development. 2005;126(2):317–26.Mi Z., Gan B., Yu S., Guo J., Zhang C., Jiang X. et al. Dual-target anti-Alzheimer’s disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity. Journal of enzyme inhibition and medicinal chemistry. 2019;34(1):1489–97.Mi Z., Gan B., Yu S., Guo J., Zhang C., Jiang X. et al. Dual-target anti-Alzheimer’s disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity. Journal of enzyme inhibition and medicinal chemistry. 2019;34(1):1489–97.Borroni E., Bohrmann B., Grueninger F., Prinssen E., Nave S., Loetscher H. et al. Sembragiline: a novel, selective monoamine oxidase type B inhibitor for the treatment of Alzheimer’s disease. Journal of Pharmacology and Experimental Therapeutics. 2017;362(3):413–23.Borroni E., Bohrmann B., Grueninger F., Prinssen E., Nave S., Loetscher H. et al. Sembragiline: a novel, selective monoamine oxidase type B inhibitor for the treatment of Alzheimer’s disease. Journal of Pharmacology and Experimental Therapeutics. 2017;362(3):413–23.Yamada M., Yasuhara H. Clinical pharmacology of MAO inhibitors: safety and future. Neurotoxicology. 2004;25(1–2):215–21.Yamada M., Yasuhara H. Clinical pharmacology of MAO inhibitors: safety and future. Neurotoxicology. 2004;25(1–2):215–21.Tariot P.N., Sunderland T., Weingartner H., Murphy D.L., Welkowitz J.A., Thompson K., Cohen R.M. Cognitive effects of L-deprenyl in Alzheimer’s disease. Psychopharmacology. 1987;91(4):489–95.Tariot P.N., Sunderland T., Weingartner H., Murphy D.L., Welkowitz J.A., Thompson K., Cohen R.M. Cognitive effects of L-deprenyl in Alzheimer’s disease. Psychopharmacology. 1987;91(4):489–95.Mangoni A., Grassi M.P., Frattola L., Piolti R., Bassi S., Motta A. et al. Effects of a MAO-B inhibitor in the treatment of Alzheimer disease. European neurology. 1991;31(2):100–7.Mangoni A., Grassi M.P., Frattola L., Piolti R., Bassi S., Motta A. et al. Effects of a MAO-B inhibitor in the treatment of Alzheimer disease. European neurology. 1991;31(2):100–7.Kavully F.S., Oh J.M., Dev S., Kaipakasseri S., Palakkathondi A., Vengamthodi A. et al. Design of enamides as new selective monoamine oxidase-B inhibitors. Journal of Pharmacy and Pharmacology. 2020;72(7):916–26.Kavully F.S., Oh J.M., Dev S., Kaipakasseri S., Palakkathondi A., Vengamthodi A. et al. Design of enamides as new selective monoamine oxidase-B inhibitors. Journal of Pharmacy and Pharmacology. 2020;72(7):916–26.Kumar M.J., Andersen J.K. Perspectives on MAO-B in aging and neurological disease. Molecular neurobiology. 2004;30(1):77–89.Kumar M.J., Andersen J.K. Perspectives on MAO-B in aging and neurological disease. Molecular neurobiology. 2004;30(1):77–89.Li Q., Yang H., Chen Y., Sun H. Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer’s disease. European journal of medicinal chemistry. 2017;132:294–309.Li Q., Yang H., Chen Y., Sun H. Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer’s disease. European journal of medicinal chemistry. 2017;132:294–309.Nordberg A., Ballard C., Bullock R., Darreh-Shori T., Somogyi M. A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease. The primary care companion for CNS disorders. 2013;15(2):26731.Nordberg A., Ballard C., Bullock R., Darreh-Shori T., Somogyi M. A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease. The primary care companion for CNS disorders. 2013;15(2):26731.Pohanka M. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity. International journal of molecular sciences. 2014;15(6):9809–25.Pohanka M. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity. International journal of molecular sciences. 2014;15(6):9809–25.Bhounsule A.S., Bhatt L.K., Prabhavalkar K.S., Oza M. Cyclin dependent kinase 5: A novel avenue for Alzheimer’s disease. Brain research bulletin. 2017;132:28–38.Bhounsule A.S., Bhatt L.K., Prabhavalkar K.S., Oza M. Cyclin dependent kinase 5: A novel avenue for Alzheimer’s disease. Brain research bulletin. 2017;132:28–38.Wei F.Y., Tomizawa K. Cyclin-dependent kinase 5 (Cdk5): a potential therapeutic target for the treatment of neurodegenerative diseases and diabetes mellitus. Mini Reviews in Medicinal Chemistry. 2007;7(10):1070–4.Wei F.Y., Tomizawa K. Cyclin-dependent kinase 5 (Cdk5): a potential therapeutic target for the treatment of neurodegenerative diseases and diabetes mellitus. Mini Reviews in Medicinal Chemistry. 2007;7(10):1070–4.Liu S.L., Wang C., Jiang T., Tan L., Xing A., Yu J.T. The role of Cdk5 in Alzheimer’s disease. Molecular neurobiology. 2016;53(7):4328–42.Liu S.L., Wang C., Jiang T., Tan L., Xing A., Yu J.T. The role of Cdk5 in Alzheimer’s disease. Molecular neurobiology. 2016;53(7):4328–42.Das B., Yan R. Role of BACE1 in Alzheimer’s synaptic function. Translational Neurodegeneration. 2017;6(1):1–8.Das B., Yan R. Role of BACE1 in Alzheimer’s synaptic function. Translational Neurodegeneration. 2017;6(1):1–8.Moussa C.E. Beta-secretase inhibitors in phase I and phase II clinical trials for Alzheimer’s disease. Expert opinion on investigational drugs. 2017;26(10):1131–6.Moussa C.E. Beta-secretase inhibitors in phase I and phase II clinical trials for Alzheimer’s disease. Expert opinion on investigational drugs. 2017;26(10):1131–6.Macalino S.J., Gosu V., Hong S., Choi S. Role of computer-aided drug design in modern drug discovery. Archives of Pharmacal research. 2015;38(9):1686–701.Macalino S.J., Gosu V., Hong S., Choi S. Role of computer-aided drug design in modern drug discovery. Archives of Pharmacal research. 2015;38(9):1686–701.Mavromoustakos T., Durdagi S., Koukoulitsa C., Simcic M., Papadopoulos M.G., Hodoscek M., Golic Grdadolnik S. Strategies in the rational drug design. Current medicinal chemistry. 2011;18(17):2517–30.Mavromoustakos T., Durdagi S., Koukoulitsa C., Simcic M., Papadopoulos M.G., Hodoscek M., Golic Grdadolnik S. Strategies in the rational drug design. Current medicinal chemistry. 2011;18(17):2517–30.Kumar N., Gahlawat A., Kumar R.N., Singh Y.P., Modi G., Garg P. Drug repurposing for Alzheimer’s disease: in silico and in vitro investigation of FDA-approved drugs as acetylcholinesterase inhibitors. Journal of Biomolecular Structure and Dynamics. 2022;40(7):2878–2892. doi: 10.1080/07391102.2020.1844054Kumar N., Gahlawat A., Kumar R.N., Singh Y.P., Modi G., Garg P. Drug repurposing for Alzheimer’s disease: in silico and in vitro investigation of FDA-approved drugs as acetylcholinesterase inhibitors. Journal of Biomolecular Structure and Dynamics. 2022;40(7):2878–2892. doi: 10.1080/07391102.2020.1844054Bauzon J., Lee G., Cummings J. Repurposed agents in the Alzheimer’s disease drug development pipeline. Alzheimer’s research & therapy. 2020;12(1):98. doi: 10.1186/s13195-020-00662-xBauzon J., Lee G., Cummings J. Repurposed agents in the Alzheimer’s disease drug development pipeline. Alzheimer’s research & therapy. 2020;12(1):98. doi: 10.1186/s13195-020-00662-xIhara M., Saito S. Drug repositioning for Alzheimer’s disease: finding hidden clues in old drugs. Journal of Alzheimer’s Disease. 2020;74(4):1013–28. doi: 10.3233/JAD-200049Ihara M., Saito S. Drug repositioning for Alzheimer’s disease: finding hidden clues in old drugs. Journal of Alzheimer’s Disease. 2020;74(4):1013–28. doi: 10.3233/JAD-200049Mayr L.M., Bojanic D. Novel trends in high-throughput screening. Current opinion in pharmacology. 2009;9(5):580–8. doi: 10.1016/j.coph.2009.08.004Mayr L.M., Bojanic D. Novel trends in high-throughput screening. Current opinion in pharmacology. 2009;9(5):580–8. doi: 10.1016/j.coph.2009.08.004Padhi, D., Govindaraju, T. Mechanistic Insights for Drug Repurposing and the Design of Hybrid Drugs for Alzheimer ’s disease. Journal of Medicinal Chemistry. 2022;65(10):7088–7105. doi: 10.1021/acs.jmedchem.2c00335Padhi, D., Govindaraju, T. Mechanistic Insights for Drug Repurposing and the Design of Hybrid Drugs for Alzheimer ’s disease. Journal of Medicinal Chemistry. 2022;65(10):7088–7105. doi: 10.1021/acs.jmedchem.2c00335Mao L., Jin H., Wang M., Hu Y., Chen S., He Q. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–690. doi: 10.1001/jamaneurol.2020.1127Mao L., Jin H., Wang M., Hu Y., Chen S., He Q. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–690. doi: 10.1001/jamaneurol.2020.1127

The authors declare that there are no conflicts of interest present.