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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Challenges and Discoveries in Polypharmacology of Neurodegenerative Diseases

Author(s): Teresa Carolliny Moreira Lustoza Rodrigues, Natália Ferreira de Sousa, Aline Matilde Ferreira dos Santos, Renan Dantas Aires Guimarães, Marcus Tullius Scotti and Luciana Scotti*

Volume 23, Issue 5, 2023

Published on: 14 February, 2023

Page: [349 - 370] Pages: 22

DOI: 10.2174/1568026623666230126112628

Price: $65

Abstract

Background: Neurological disorders are composed of several diseases that affect the central and peripheral nervous system; among these are neurodegenerative diseases, which lead to neuronal death. Many of these diseases have treatment for the disease and symptoms, leading patients to use several drugs that cause side effects.

Introduction: The search for new treatments has led to the investigation of multi-target drugs.

Methods: This review aimed to investigate in the literature the multi-target effect in neurological disorders through an in silico approach. Studies were reviewed on the diseases such as epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS), Huntington's disease, cerebral ischemia, and Parkinson's disease.

Results: As a result, the study emphasize the relevance of research by computational techniques such as quantitative structure-activity relationship (QSAR) prediction models, pharmacokinetic prediction models, molecular docking, and molecular dynamics, besides presenting possible drug candidates with multi-target activity.

Conclusion: It was possible to identify several targets with pharmacological activities. Some of these targets had diseases in common such as carbonic anhydrase, acetylcholinesterase, NMDA, and MAO being relevant for possible multi-target approaches.

Keywords: In silico, Polypharmacology, Neurodegenerative disease, Docking, Drug target, Neurological disorders.

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[1]
Pan American Health Organization. The burden of Neurological conditions in the Region of the Americas, 2000-2019/ Available from: https://www.paho.org/en/noncommunicable-diseases-and-mental-health/noncommunicable-diseases-and-mental-health-data-portal-3
[2]
Shou, J.W.; Shaw, P.C. Therapeutic efficacies of berberine against neurological disorders: an update of pharmacological effects and mechanisms. Cells, 2022, 11(5), 796.
[http://dx.doi.org/10.3390/cells11050796] [PMID: 35269418]
[3]
Feigin, V.L.; Vos, T. Global Burden of Neurological Disorders: From global burden of disease estimates to actions. Neuroepidemiology, 2019, 52(1-2), 1-2.
[http://dx.doi.org/10.1159/000495197] [PMID: 30472717]
[4]
Storey, C.L.; Williams, R.S.B.; Fisher, P.R.; Annesley, S.J. Dictyostelium discoideum: A model system for neurological disorders. Cells, 2022, 11, 463.
[http://dx.doi.org/10.3390/cells11030463]
[5]
Ahani-Nahayati, M.; Shariati, A.; Mahmoodi, M.; Olegovna Zekiy, A.; Javidi, K.; Shamlou, S.; Mousakhani, A.; Zamani, M.; Hassanzadeh, A. Stem cell in neurodegenerative disorders; an emerging strategy. Int. J. Dev. Neurosci., 2021, 81(4), 291-311.
[http://dx.doi.org/10.1002/jdn.10101] [PMID: 33650716]
[6]
Astillero-Lopez, V.; Gonzalez-Rodriguez, M.; Villar-Conde, S.; Flores-Cuadrado, A.; Martinez-Marcos, A.; Ubeda-Banon, I.; Saiz-Sanchez, D. Neurodegeneration and astrogliosis in the entorhinal cortex in Alzheimer’s disease: Stereological layer‐specific assessment and proteomic analysis. Alzheimers Dement., 2022, 18(12), 2468-2480.
[http://dx.doi.org/10.1002/alz.12580] [PMID: 35142030]
[7]
Callahan, J.W.; Wokosin, D.L.; Bevan, M.D. Dysregulation of the basal ganglia indirect pathway in early symptomatic Q175 huntington’s disease mice. J. Neurosci., 2022, 42(10), 2080-2102.
[http://dx.doi.org/10.1523/JNEUROSCI.0782-21.2022] [PMID: 35058372]
[8]
Adachi, T.; Hanajima, R. Neuropathological changes in advanced Parkinson’s disease. Neurol. Clin. Neurosci., 2022, ncn3.12596.
[http://dx.doi.org/10.1111/ncn3.12596]
[9]
Essawy, A.E.; El-Sayed, S.A.; Tousson, E. Abd El-gawad, H.S.; Alhasani, R.H.; Abd Elkader, H.T.A.E. Anti-kindling effect of ginkgo biloba leaf extract and L-Carnitine in the pentylenetetrazol model of epilepsy. Environ. Sci. Pollut. Res. Int., 2022, 1-15.
[http://dx.doi.org/10.1007/S11356-022-19251-6/FIGURES/9]
[10]
Li, T.H.; Sun, H.W.; Song, L.J.; Yang, B.; Zhang, P.; Yan, D.M.; Liu, X.Z.; Luo, Y.R. Long non-coding RNA MEG3 regulates autophagy after cerebral ischemia/reperfusion injury. Neural Regen. Res., 2022, 17(4), 824-831.
[http://dx.doi.org/10.4103/1673-5374.322466] [PMID: 34472482]
[11]
You, J.; Maksimovic, K.; Lee, J.; Khan, M.; Masuda, R.; Park, J. Selective Loss of MATR3 in spinal interneurons, upper motor neurons and Hippocampal CA1 neurons in a MATR3 S85C knock-in mouse model of amyotrophic lateral sclerosis. Biology, 2022, 11(2), 298.
[http://dx.doi.org/10.3390/biology11020298]
[12]
Zhao, N.; Quicksall, Z.; Asmann, Y.W.; Ren, Y. Network approaches for omics studies of neurodegenerative diseases. Front. Genet., 2022, 13, 984338.
[http://dx.doi.org/10.3389/fgene.2022.984338] [PMID: 36186441]
[13]
Cagin, U. Targeting age-related neurodegenerative diseases by AAV-Mediated gene therapy. Adv. Exp. Med. Biol., 2021, 1286, 213-223.
[http://dx.doi.org/10.1007/978-3-030-55035-6_15] [PMID: 33725356]
[14]
Sun, J.; Roy, S. Gene-based therapies for neurodegenerative diseases. Nat. Neurosci., 2021, 24(3), 297-311.
[http://dx.doi.org/10.1038/s41593-020-00778-1]
[15]
Vuletić V.; Rački, V.; Papić E.; Peterlin, B. A systematic review of parkinson’s disease pharmacogenomics: Is there time for translation into the clinics? Int. J. Mol. Sci., 2021, 22(13), 7213.
[http://dx.doi.org/10.3390/ijms22137213]
[16]
Mortada, I.; Farah, R.; Nabha, S.; Ojcius, D.M.; Fares, Y.; Almawi, W.Y.; Sadier, N.S. Immunotherapies for neurodegenerative diseases. Front. Neurol., 2021, 12, 654739.
[http://dx.doi.org/10.3389/fneur.2021.654739] [PMID: 34163421]
[17]
Puranik, N.; Yadav, D.; Chauhan, P.S.; Kwak, M.; Jin, J.O. Exploring the role of gene therapy for neurological disorders. Curr. Gene Ther., 2021, 21(1), 11-22.
[http://dx.doi.org/10.2174/1566523220999200917114101] [PMID: 32940177]
[18]
Tomaselli, D.; Lucidi, A.; Rotili, D.; Mai, A. Epigenetic polypharmacology: A new frontier for epi‐drug discovery. Med. Res. Rev., 2020, 40(1), 190-244.
[http://dx.doi.org/10.1002/med.21600] [PMID: 31218726]
[19]
Nam, S.; Lee, S.; Park, S.; Lee, J.; Park, A.; Kim, Y.H.; Park, T. PATHOME-Drug: a subpathway-based polypharmacology drug-repositioning method. Bioinformatics, 2022, 38(2), 444-452.
[http://dx.doi.org/10.1093/bioinformatics/btab566] [PMID: 34515762]
[20]
Pinzi, L.; Tinivella, A.; Caporuscio, F.; Rastelli, G. Drug repurposing and polypharmacology to fight SARS-CoV-2 through inhibition of the main protease. Front. Pharmacol., 2021, 12, 636989.
[http://dx.doi.org/10.3389/fphar.2021.636989] [PMID: 33692695]
[21]
Chaudhari, R.; Fong, L.W.; Tan, Z.; Huang, B.; Zhang, S. An up-to-date overview of computational polypharmacology in modern drug discovery. Expert Opin. Drug Discov., 2020, 15(9), 1025-1044.
[http://dx.doi.org/10.1080/17460441.2020.1767063] [PMID: 32452701]
[22]
Müller, B.; Castro, L.J.; Rebholz-Schuhmann, D. Ontology-based identification and prioritization of candidate drugs for epilepsy from literature. J. Biomed. Semantics, 2022, 13(1), 3.
[http://dx.doi.org/10.1186/s13326-021-00258-w] [PMID: 35073996]
[23]
Advani, D.; Gupta, R.; Tripathi, R.; Sharma, S.; Ambasta, R.K.; Kumar, P. Protective role of anticancer drugs in neurodegenerative disorders: A drug repurposing approach. Neurochem. Int., 2020, 140, 104841.
[http://dx.doi.org/10.1016/j.neuint.2020.104841] [PMID: 32853752]
[24]
Shah, S.; Dooms, M.M.; Amaral-Garcia, S.; Igoillo-Esteve, M. Current drug repurposing strategies for rare neurodegenerative disorders. Front. Pharmacol., 2021, 12, 768023.
[http://dx.doi.org/10.3389/fphar.2021.768023] [PMID: 34992533]
[25]
Sharma, S.; Nozohouri, S.; Vaidya, B.; Abbruscato, T. Repurposing metformin to treat age-related neurodegenerative disorders and ischemic stroke. Life Sci., 2021, 274, 119343.
[http://dx.doi.org/10.1016/j.lfs.2021.119343] [PMID: 33716063]
[26]
Bhagat, R.T.; Butle, S.R. Drug repurposing: A review. J. Pharm. Res. Int., 2021, 161-169.
[http://dx.doi.org/10.9734/jpri/2021/v33i31B31704]
[27]
Urbina, F.; Puhl, A.C.; Ekins, S. Recent advances in drug repurposing using machine learning. Curr. Opin. Chem. Biol., 2021, 65, 74-84.
[http://dx.doi.org/10.1016/j.cbpa.2021.06.001] [PMID: 34274565]
[28]
Rodriguez, S.; Hug, C.; Todorov, P.; Moret, N.; Boswell, S.A.; Evans, K.; Zhou, G.; Johnson, N.T.; Hyman, B.T.; Sorger, P.K.; Albers, M.W.; Sokolov, A. Machine learning identifies candidates for drug repurposing in Alzheimer’s Disease. Nat. Commun., 2021, 12(1), 1-13.
[http://dx.doi.org/10.1038/s41467-021-21330-0]
[29]
Hadlandsmyth, K.; Bernardy, N.C.; Lund, B.C. Central nervous system polytherapy among veterans with posttraumatic stress disorder: Changes across a decade. Gen. Hosp. Psychiatry, 2022, 74, 46-50.
[http://dx.doi.org/10.1016/j.genhosppsych.2021.12.002] [PMID: 34906798]
[30]
Dabla, P.K.; Sharma, S.; Mir, R.; Puri, V. Significant association of antiepileptic drug polytherapy with decreased FT4 levels in epileptic patients. Indian J. Clin. Biochem., 2022, 37(1), 107-112.
[http://dx.doi.org/10.1007/s12291-020-00946-x] [PMID: 35125700]
[31]
Kang, Y.; Jeong, B.; Lim, D.H.; Lee, D.; Lim, K.M. In silico prediction of the full united nations globally harmonized system eye irritation categories of liquid chemicals by iata-like bottom-up approach of random forest method. J. Toxicol. Environ. Health A, 2021, 84(23), 960-972.
[http://dx.doi.org/10.1080/15287394.2021.1956661]
[32]
Llorach-Pares, L.; Nonell-Canals, A.; Avila, C.; Sanchez-Martinez, M. Computer-Aided Drug Design (CADD) to De-Orphanize marine molecules: Finding potential therapeutic agents for neurodegenerative and cardiovascular diseases. Mar. Drugs, 2022, 20(1), 53.
[http://dx.doi.org/10.3390/md20010053] [PMID: 35049908]
[33]
Olasupo, S.B.; Uzairu, A.; Shallangwa, G.A.; Uba, S. Computer-aided drug design and in silico pharmacokinetics predictions of some potential antipsychotic agents. Sci. Am., 2021, 12, e00734.
[http://dx.doi.org/10.1016/j.sciaf.2021.e00734]
[34]
World Health Organization (WHO). Expert Committee on Drug Dependence. WHO Expert Committee on Drug Dependence: fortieth report, Available from: https://apps.who.int/iris/handle/10665/279948 [Accessed on: May 28, 2022].
[35]
Thijs, R.D.; Surges, R.; O’Brien, T.J.; Sander, J.W. Epilepsy in adults. Lancet, 2019, 393(10172), 689-701.
[http://dx.doi.org/10.1016/S0140-6736(18)32596-0] [PMID: 30686584]
[36]
Falco-Walter, J. Epilepsy-definition, classification, pathophysiology, and epidemiology. Semin. Neurol., 2020, 40(6), 617-623.
[http://dx.doi.org/10.1055/s-0040-1718719] [PMID: 33155183]
[37]
Perucca, P.; Scheffer, I.E.; Kiley, M. The management of epilepsy in children and adults. Med. J. Aust., 2018, 208(5), 226-233.
[http://dx.doi.org/10.5694/mja17.00951] [PMID: 29540143]
[38]
Löscher, W. Single-Target versus multi-target drugs versus combinations of drugs with multiple targets: Preclinical and clinical evidence for the treatment or prevention of epilepsy. Front. Pharmacol., 2021, 12, 730257.
[http://dx.doi.org/10.3389/fphar.2021.730257] [PMID: 34776956]
[39]
Valipour, M.; Naderi, N.; Heidarli, E.; Shaki, F.; Motafeghi, F.; Talebpour Amiri, F.; Emami, S.; Irannejad, H. Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: A comprehensive in silico, in vitro, and in vivo study. Eur. J. Pharm. Sci., 2021, 166, 105974.
[http://dx.doi.org/10.1016/j.ejps.2021.105974] [PMID: 34390829]
[40]
Rampogu, S.; Park, S.J.; Lee, K.W.; Baek, A.; Bavi, R.; Son, M.; Cao, G.P.; Kumar, R.; Park, C.; Zeb, A.; Rana, R.M. Identification of novel scaffolds with dual role as antiepileptic and anti-breast cancer. IEEE/ACM Trans. Comput. Biol. Bioinform., 2019, 16(5), 1663-1674.
[http://dx.doi.org/10.1109/TCBB.2018.2855138] [PMID: 30334765]
[41]
Türkeş C.; Arslan, M.; Demir, Y.; Çoçaj, L.; Rifati Nixha, A.; Beydemir, Ş. Synthesis, biological evaluation and in silico studies of novel N-substituted phthalazine sulfonamide compounds as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg. Chem., 2019, 89, 103004.
[http://dx.doi.org/10.1016/j.bioorg.2019.103004] [PMID: 31129502]
[42]
Nadaroglu, H.; Gungor, A.A.; Gundogdu, Ö.; Kishali, N.H.; Sever, B.; Altintop, M.D. Investigation of the inhibitory effects of isoindoline-1,3-dion derivatives on hCA-I and hCA-II enzyme activities. J. Mol. Struct., 2019, 1197, 386-392.
[http://dx.doi.org/10.1016/j.molstruc.2019.07.070]
[43]
Bayindir, S.; Caglayan, C.; Karaman, M. Gülcin, İ. The green synthesis and molecular docking of novel N-substituted rhodanines as effective inhibitors for carbonic anhydrase and acetylcholinesterase enzymes. Bioorg. Chem., 2019, 90, 103096.
[http://dx.doi.org/10.1016/j.bioorg.2019.103096] [PMID: 31284100]
[44]
Emami, S.; Valipour, M.; Kazemi Komishani, F.; Sadati-Ashrafi, F.; Rasoulian, M.; Ghasemian, M.; Tajbakhsh, M.; Honarchian Masihi, P.; Shakiba, A.; Irannejad, H.; Ahangar, N. Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents. Bioorg. Chem., 2021, 112(112), 104943.
[http://dx.doi.org/10.1016/j.bioorg.2021.104943] [PMID: 33964578]
[45]
Lopez, O.L.; Kuller, L.H. Epidemiology of aging and associated cognitive disorders: Prevalence and incidence of Alzheimer’s disease and other dementias. Handb. Clin. Neurol., 2019, 167, 139-148.
[http://dx.doi.org/10.1016/B978-0-12-804766-8.00009-1] [PMID: 31753130]
[46]
Frisoni, G.B.; Altomare, D.; Thal, D.R.; Ribaldi, F.; van der Kant, R.; Ossenkoppele, R.; Blennow, K.; Cummings, J.; van Duijn, C.; Nilsson, P.M.; Dietrich, P.Y.; Scheltens, P.; Dubois, B. The probabilistic model of Alzheimer disease: the amyloid hypothesis revised. Nat. Rev. Neurosci., 2022, 23(1), 53-66.
[http://dx.doi.org/10.1038/s41583-021-00533-w] [PMID: 34815562]
[47]
Kumar, V.; Kundu, S.; Singh, A.; Singh, S. Understanding the role of histone deacetylase and their inhibitors in neurodegenerative disorders: Current targets and future perspective. Curr. Neuropharmacol., 2022, 20(1), 158-178.
[http://dx.doi.org/10.2174/1570159X19666210609160017] [PMID: 34151764]
[48]
Sobko, A. Cell Biologist’s Perspective: Frontiers in Development of PROTAC-Mediated HDAC Degraders; OSF Prepr; , 2021. INCOMPLETE
[49]
Rodrigues, D.A.; Pinheiro, P.S.M.; Sagrillo, F.S.; Bolognesi, M.L.; Fraga, C.A.M. Histone deacetylases as targets for the treatment of neurodegenerative disorders: Challenges and future opportunities. Med. Res. Rev., 2020, 40(6), 2177-2211.
[http://dx.doi.org/10.1002/med.21701] [PMID: 32588916]
[50]
Tseng, H.J.; Lin, M.H.; Shiao, Y.J.; Yang, Y.C.; Chu, J.C.; Chen, C.Y.; Chen, Y.Y.; Lin, T.E.; Su, C.J.; Pan, S.L.; Chen, L.C.; Wang, C.Y.; Hsu, K.C.; Huang, W.J. Synthesis and biological evaluation of acridine-based histone deacetylase inhibitors as multitarget agents against Alzheimer’s disease. Eur. J. Med. Chem., 2020, 192, 112193.
[http://dx.doi.org/10.1016/j.ejmech.2020.112193] [PMID: 32151835]
[51]
Rodrigues, D.A.; Pinheiro, P.S.M.; Fraga, C.A.M. Multitarget Inhibition of Histone Deacetylase (HDAC) and Phosphatidylinositol‐3‐kinase (PI3K): Current and future prospects. ChemMedChem, 2021, 16(3), 448-457.
[http://dx.doi.org/10.1002/cmdc.202000643] [PMID: 33049098]
[52]
De Simone, A.; Milelli, A. Histone deacetylase inhibitors as multitarget ligands: New players in Alzheimer’s disease drug discovery? ChemMedChem, 2019, 14(11), 1067-1073.
[http://dx.doi.org/10.1002/cmdc.201900174] [PMID: 30958639]
[53]
Briggs, R.; Kennelly, S.P.; O’Neill, D. Drug treatments in Alzheimer’s disease. Clin. Med. (Lond.), 2016, 16(3), 247-253.
[http://dx.doi.org/10.7861/clinmedicine.16-3-247] [PMID: 27251914]
[54]
Cummings, J.L.; Tong, G.; Ballard, C. Treatment Combinations for Alzheimer’s Disease: Current and future pharmacotherapy options. J. Alzheimers Dis., 2019, 67(3), 779-794.
[http://dx.doi.org/10.3233/JAD-180766] [PMID: 30689575]
[55]
Benek, O.; Korabecny, J.; Soukup, O. A perspective on multi-target drugs for Alzheimer’s Disease. Trends Pharmacol. Sci., 2020, 41(7), 434-445.
[http://dx.doi.org/10.1016/j.tips.2020.04.008] [PMID: 32448557]
[56]
Soares Romeiro, L.A.; da Costa Nunes, J.L.; de Oliveira Miranda, C.; Simões Heyn Roth Cardoso, G.; de Oliveira, A.S.; Gandini, A.; Kobrlova, T.; Soukup, O.; Rossi, M.; Senger, J.; Jung, M.; Gervasoni, S.; Vistoli, G.; Petralla, S.; Massenzio, F.; Monti, B.; Bolognesi, M.L. Novel sustainable-by-Design HDAC inhibitors for the treatment of Alzheimer’s Disease. ACS Med. Chem. Lett., 2019, 10(4), 671-676.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00071] [PMID: 30996816]
[57]
Athira, K.V.; Sadanandan, P.; Chakravarty, S. Repurposing vorinostat for the treatment of disorders affecting brain. NeuroMol. Med., 2021, 23(4), 449-465.
[http://dx.doi.org/10.1007/s12017-021-08660-4]
[58]
Kilgore, M.; Miller, C.A.; Fass, D.M.; Hennig, K.M.; Haggarty, S.J.; Sweatt, J.D.; Rumbaugh, G. Inhibitors of Class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s Disease. Neuropsychopharmacol., 2010, 35(4), 870-880.
[http://dx.doi.org/10.1038/npp.2009.197]
[59]
Neganova, M.; Aleksandrova, Y.; Suslov, E.; Mozhaitsev, E.; Munkuev, A.; Tsypyshev, D.; Chicheva, M.; Rogachev, A.; Sukocheva, O.; Volcho, K.; Klochkov, S. Novel multitarget hydroxamic acids with a natural origin CAP group against Alzheimer’s Disease: Synthesis, docking and biological evaluation. Pharmaceutics, 2021, 13(11), 1893.
[http://dx.doi.org/10.3390/pharmaceutics13111893] [PMID: 34834312]
[60]
Mishra, C.B.; Shalini, S.; Gusain, S.; Prakash, A.; Kumari, J.; Kumari, S.; Yadav, A.K.; Lynn, A.M.; Tiwari, M. Development of novel N -(6-methanesulfonyl-benzothiazol-2-yl)-3-(4-substituted-piperazin-1-yl)-propionamides with cholinesterase inhibition, anti-β-amyloid aggregation, neuroprotection and cognition enhancing properties for the therapy of Alzheimer’s disease. RSC Advances, 2020, 10(30), 17602-17619.
[http://dx.doi.org/10.1039/D0RA00663G] [PMID: 35515597]
[61]
Kalaycı M.; Türkeş C.; Arslan, M.; Demir, Y.; Beydemir, Ş. Novel benzoic acid derivatives: Synthesis and biological evaluation as multitarget acetylcholinesterase and carbonic anhydrase inhibitors. Arch. Pharm. (Weinheim), 2021, 354(3), 2000282.
[http://dx.doi.org/10.1002/ardp.202000282] [PMID: 33155700]
[62]
Titov, A.A.; Kobzev, M.S.; Catto, M.; Candia, M.; Gambacorta, N.; Denora, N.; Pisani, L.; Nicolotti, O.; Borisova, T.N.; Varlamov, A.V.; Voskressensky, L.G.; Altomare, C.D. Away from Flatness: Unprecedented Nitrogen-Bridged Cyclopenta[ a]indene Derivatives as Novel Anti-Alzheimer Multitarget Agents. ACS Chem. Neurosci., 2021, 12(2), 340-353.
[http://dx.doi.org/10.1021/acschemneuro.0c00706] [PMID: 33395258]
[63]
Patel, D.V.; Patel, N.R.; Kanhed, A.M.; Teli, D.M.; Patel, K.B.; Gandhi, P.M.; Patel, S.P.; Chaudhary, B.N.; Shah, D.B.; Prajapati, N.K.; Patel, K.V.; Yadav, M.R. Further studies on triazinoindoles as potential novel multitarget-directed anti-Alzheimer’s agents. ACS Chem. Neurosci., 2020, 11(21), 3557-3574.
[http://dx.doi.org/10.1021/acschemneuro.0c00448] [PMID: 33073564]
[64]
Iqbal, D.; Rehman, M.T.; Bin Dukhyil, A.; Rizvi, S.M.D.; Al Ajmi, M.F.; Alshehri, B.M.; Banawas, S.; Khan, M.S.; Alturaiki, W.; Alsaweed, M. High-throughput screening and molecular dynamics simulation of natural product-like compounds against Alzheimer’s Disease through multitarget approach. Pharmaceuticals (Basel), 2021, 14(9), 937.
[http://dx.doi.org/10.3390/ph14090937] [PMID: 34577637]
[65]
Sánchez Montero, J.M.; Agis-Torres, A.; Solano, D.; Söllhuber, M.; Fernandez, M.; Villaro, W.; Gómez-Cañas, M.; García-Arencibia, M.; Fernández-Ruiz, J.; Egea, J.; Martín, M.I.; Girón, R. Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer’s disease. Eur. J. Pharmacol., 2021, 895, 173875.
[http://dx.doi.org/10.1016/j.ejphar.2021.173875] [PMID: 33460612]
[66]
Patel, D.V.; Patel, N.R.; Kanhed, A.M.; Teli, D.M.; Patel, K.B.; Joshi, P.D.; Patel, S.P.; Gandhi, P.M.; Chaudhary, B.N.; Prajapati, N.K.; Patel, K.V.; Yadav, M.R. Novel carbazole-stilbene hybrids as multifunctional anti-Alzheimer agents. Bioorg. Chem., 2020, 101, 103977.
[http://dx.doi.org/10.1016/j.bioorg.2020.103977] [PMID: 32485470]
[67]
Choubey, P.K.; Tripathi, A.; Sharma, P.; Shrivastava, S.K. Design, synthesis, and multitargeted profiling of N-benzylpyrrolidine derivatives for the treatment of Alzheimer’s disease. Bioorg. Med. Chem., 2020, 28(22), 115721.
[http://dx.doi.org/10.1016/j.bmc.2020.115721] [PMID: 33007563]
[68]
Liu, Z.; Shi, Y.; Zhang, X.; Yu, G.; Li, J.; Cong, S.; Deng, Y. Discovery of novel 3-butyl-6-benzyloxyphthalide Mannich base derivatives as multifunctional agents against Alzheimer’s disease. Bioorg. Med. Chem., 2022, 58, 116660.
[http://dx.doi.org/10.1016/j.bmc.2022.116660] [PMID: 35183029]
[69]
Remya, C.; Dileep, K.V.; Koti Reddy, E.; Mantosh, K.; Lakshmi, K.; Sarah Jacob, R.; Sajith, A.M.; Jayadevi Variyar, E.; Anwar, S.; Zhang, K.Y.J.; Sadasivan, C.; Omkumar, R.V. Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase – Design, synthesis and biological evaluation. Comput. Struct. Biotechnol. J., 2021, 19, 4517-4537.
[http://dx.doi.org/10.1016/j.csbj.2021.07.041] [PMID: 34471497]
[70]
Namasivayam, V.; Stefan, K.; Pahnke, J.; Stefan, S.M. Binding mode analysis of ABCA7 for the prediction of novel Alzheimer’s disease therapeutics. Comput. Struct. Biotechnol. J., 2021, 19, 6490-6504.
[http://dx.doi.org/10.1016/j.csbj.2021.11.035] [PMID: 34976306]
[71]
Elbatrawy, A.A.; Hyeon, S.J.; Yue, N.; Osman, E.E.A.; Choi, S.H.; Lim, S.; Kim, Y.K.; Ryu, H.; Cui, M.; Nam, G. “Turn-On” Quinoline-Based fluorescent probe for selective imaging of tau aggregates in Alzheimer’s Disease: Rational design, synthesis, and molecular docking. ACS Sens., 2021, 6(6), 2281-2289.
[http://dx.doi.org/10.1021/acssensors.1c00338] [PMID: 34115933]
[72]
Hung, T.M.; Lee, J.S.; Chuong, N.N.; Kim, J.A.; Oh, S.H.; Woo, M.H.; Choi, J.S.; Min, B.S. Kinetics and molecular docking studies of cholinesterase inhibitors derived from water layer of Lycopodiella cernua (L.) Pic. Serm. (II). Chem. Biol. Interact., 2015, 240, 74-82.
[http://dx.doi.org/10.1016/j.cbi.2015.07.008] [PMID: 26297990]
[73]
van den Bos, M.A.J.; Geevasinga, N.; Higashihara, M.; Menon, P.; Vucic, S. Pathophysiology and diagnosis of ALS: Insights from advances in neurophysiological techniques. Int. J. Mol. Sci., 2019, 20(11), 2818.
[http://dx.doi.org/10.3390/ijms20112818] [PMID: 31185581]
[74]
Norris, S.P.; Likanje, M.F.N.; Andrews, J.A. Amyotrophic lateral sclerosis: Update on clinical management. Curr. Opin. Neurol., 2020, 33(5), 641-648.
[http://dx.doi.org/10.1097/WCO.0000000000000864] [PMID: 32868602]
[75]
Chiò, A.; Mazzini, L.; Mora, G. Disease-modifying therapies in amyotrophic lateral sclerosis. Neuropharmacology, 2020, 167, 107986.
[http://dx.doi.org/10.1016/j.neuropharm.2020.107986] [PMID: 32062193]
[76]
Girdhar, A.; Bharathi, V.; Tiwari, V.R.; Abhishek, S.; Deeksha, W.; Mahawar, U.S.; Raju, G.; Singh, S.K.; Prabusankar, G.; Rajakumara, E.; Patel, B.K. Computational insights into mechanism of AIM4-mediated inhibition of aggregation of TDP-43 protein implicated in ALS and evidence for in vitro inhibition of liquid-liquid phase separation (LLPS) of TDP-432C-A315T by AIM4. Int. J. Biol. Macromol., 2020, 147, 117-130.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.032] [PMID: 31917988]
[77]
Martín-Cámara, O.; Arribas, M.; Wells, G.; Morales-Tenorio, M.; Martín-Requero, Á.; Porras, G.; Martínez, A.; Giorgi, G.; López-Alvarado, P.; Lastres-Becker, I.; Menéndez, J.C. Multitarget Hybrid fasudil derivatives as a new approach to the potential treatment of amyotrophic lateral sclerosis. J. Med. Chem., 2022, 65(3), 1867-1882.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01255] [PMID: 34985276]
[78]
Slota, J.A.; Medina, S.J.; Frost, K.L.; Booth, S.A. Neurons and astrocytes elicit brain region specific transcriptional responses to prion disease in the murine CA1 and thalamus. Front. Neurosci., 2022, 16, 918811.
[http://dx.doi.org/10.3389/fnins.2022.918811] [PMID: 35651626]
[79]
Li, B.; Chen, M.; Zhu, C. Neuroinflammation in prion disease. Int. J. Mol. Sci., 2021, 22(4), 2196.
[http://dx.doi.org/10.3390/ijms22042196]
[80]
Kandel, E.R. The Disordered Mind: What Unusual Brains Tell Us about Ourselves; Hachette UK, 2018.
[81]
Salem, A.; Wilson, C.J.; Rutledge, B.S.; Dilliott, A.; Farhan, S.; Choy, W.Y.; Duennwald, M.L. Matrin3: Disorder and ALS pathogenesis. Front. Mol. Biosci., 2022, 8, 794646.
[http://dx.doi.org/10.3389/fmolb.2021.794646] [PMID: 35083279]
[82]
Hu, L.; Mao, S.; Lin, L.; Bai, G.; Liu, B.; Mao, J. Stress granules in the spinal muscular atrophy and amyotrophic lateral sclerosis: The correlation and promising therapy. Neurobiol. Dis., 2022, 170, 105749.
[http://dx.doi.org/10.1016/j.nbd.2022.105749] [PMID: 35568100]
[83]
Rodrigues, D.A.; Roe, A.; Griffith, D.; Chonghaile, T.N. Advances in the design and development of PROTAC-mediated HDAC degradation. Curr. Top. Med. Chem., 2022, 22(5), 408-424.
[http://dx.doi.org/10.2174/1568026621666211015092047] [PMID: 34649488]
[84]
Wang, C.; Zhang, Y.; Wu, Y.; Xing, D. Developments of CRBN-based PROTACs as potential therapeutic agents. Eur. J. Med. Chem., 2021, 225, 113749.
[http://dx.doi.org/10.1016/j.ejmech.2021.113749] [PMID: 34411892]
[85]
Kong, X.Y.; Guan, J.; Wang, R.Z. Molecular biological roles of oxidative stress in acute brain ischemia. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2016, 38(2), 222-227.
[http://dx.doi.org/10.3881/J.ISSN.1000-503X.2016.02.017] [PMID: 27181902]
[86]
Yang, J. The role of reactive oxygen species in angiogenesis and preventing tissue injury after brain ischemia. Microvasc. Res., 2019, 123, 62-67.
[http://dx.doi.org/10.1016/j.mvr.2018.12.005] [PMID: 30594490]
[87]
Kannan, A.; Delgardo, M.; Pennington-FitzGerald, W.; Jiang, E.X.; Christophe, B.R.; Connolly, E.S., Jr Pharmacological management of cerebral ischemia in the elderly. Expert Opin. Pharmacother., 2021, 22(7), 897-906.
[http://dx.doi.org/10.1080/14656566.2020.1856815] [PMID: 33382005]
[88]
Xiong, L.; Liu, S.C.; Huo, S.Y.; Pu, L.Q.; Li, J.J.; Bai, W.Y.; Yang, Y.; Shao, J.L. Exploration in the therapeutic and multi-target mechanism of ketamine on cerebral ischemia based on network pharmacology and molecular docking. Int. J. Gen. Med., 2022, 15, 4195-4208.
[http://dx.doi.org/10.2147/IJGM.S345884] [PMID: 35480991]
[89]
Nuñez-Figueredo, Y.; Ramírez-Sánchez, J.; Pardo Andreu, G.L.; Ochoa-Rodríguez, E.; Verdecia-Reyes, Y.; Souza, D.O. Multi-targeting effects of a new synthetic molecule (JM-20) in experimental models of cerebral ischemia. Pharmacol. Rep., 2018, 70(4), 699-704.
[http://dx.doi.org/10.1016/j.pharep.2018.02.013] [PMID: 29933207]
[90]
Rocchi, D.; Blázquez-Barbadillo, C.; Agamennone, M.; Laghezza, A.; Tortorella, P.; Vicente-Zurdo, D.; Rosales-Conrado, N.; Moyano, P.; Pino, J.; González, J.F.; Menéndez, J.C. Discovery of 7-aminophenanthridin-6-one as a new scaffold for matrix metalloproteinase inhibitors with multitarget neuroprotective activity. Eur. J. Med. Chem., 2021, 210, 113061.
[http://dx.doi.org/10.1016/j.ejmech.2020.113061] [PMID: 33310289]
[91]
Hu, H.; Zhou, S.; Sun, X.; Xue, Y.; Yan, L.; Sun, X.; Lei, M.; Li, J.; Zeng, X.; Hao, L. A potent antiarrhythmic drug N-methyl berbamine extends the action potential through inhibiting both calcium and potassium currents. J. Pharmacol. Sci., 2020, 142(4), 131-139.
[http://dx.doi.org/10.1016/j.jphs.2019.12.008] [PMID: 31992491]
[92]
Kumar, G.; Mukherjee, S.; Paliwal, P.; Singh, S. Sen; Birla, H.; Singh, S. P.; Krishnamurthy, S.; Patnaik, R. Neuroprotective effect of chlorogenic acid in global cerebral ischemia-reperfusion rat model. Naunyn Schmiedeberg’s Arch. Pharmacol., 2019, 392(10), 1293-1309.
[http://dx.doi.org/10.1007/s00210-019-01670-x]
[93]
Gao, Q.; Han, Z.Y.; Tian, D.F.; Liu, G.L.; Wang, Z.Y.; Lin, J.F.; Chang, Z.; Zhang, D.D.; Xie, Y.Z.; Sun, Y.K.; Yao, X.W.; Ma, D.Y. Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology. Chin. J. Nat. Med., 2021, 19(12), 881-899.
[http://dx.doi.org/10.1016/S1875-5364(21)60079-1] [PMID: 34961587]
[94]
Goh, A.M.Y.; Wibawa, P.; Loi, S.M.; Walterfang, M.; Velakoulis, D.; Looi, J.C.L. Huntington’s disease: Neuropsychiatric manifestations of Huntington’s disease. Australas. Psychiatry, 2018, 26(4), 366-375.
[http://dx.doi.org/10.1177/1039856218791036] [PMID: 30012004]
[95]
Tabrizi, S.J.; Flower, M.D.; Ross, C.A.; Wild, E.J. Huntington disease: New insights into molecular pathogenesis and therapeutic opportunities. Nat. Rev. Neurol., 2020, 16(10), 529-546.
[http://dx.doi.org/10.1038/s41582-020-0389-4] [PMID: 32796930]
[96]
Wild, E.J.; Tabrizi, S.J. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol., 2017, 16(10), 837-847.
[http://dx.doi.org/10.1016/S1474-4422(17)30280-6] [PMID: 28920889]
[97]
Saavedra, A.; García-Díaz Barriga, G.; Pérez-Navarro, E.; Alberch, J. Huntington’s disease: Novel therapeutic perspectives hanging in the balance. Expert Opin. Ther. Targets, 2018, 22(5), 385-399.
[http://dx.doi.org/10.1080/14728222.2018.1465930] [PMID: 29671352]
[98]
Dai, W.; Chen, H.Y.; Chen, C.Y.C. A network pharmacology-based approach to investigate the novel TCM Formula against Huntington’s Disease and validated by support vector machine model. Evid. Based Complement. Alternat. Med., 2018, 2018, 6020197.
[http://dx.doi.org/10.1155/2018/6020197] [PMID: 30643534]
[99]
Raza, C.; Anjum, R.; Shakeel, N.A. Parkinson’s disease: Mechanisms, translational models and management strategies. Life Sci., 2019, 226, 77-90.
[http://dx.doi.org/10.1016/j.lfs.2019.03.057] [PMID: 30980848]
[100]
Cerri, S.; Mus, L.; Blandini, F. Parkinson’s disease in women and men: What’s the difference? J. Parkinsons Dis., 2019, 9(3), 501-515.
[http://dx.doi.org/10.3233/JPD-191683] [PMID: 31282427]
[101]
Mahoney-Sánchez, L.; Bouchaoui, H.; Ayton, S.; Devos, D.; Duce, J.A.; Devedjian, J.C. Ferroptosis and its potential role in the physiopathology of Parkinson’s Disease. Prog. Neurobiol., 2021, 196, 101890.
[http://dx.doi.org/10.1016/j.pneurobio.2020.101890] [PMID: 32726602]
[102]
Yan, N.; Zhang, J. Iron metabolism, ferroptosis, and the links with Alzheimer’s disease. Front. Neurosci., 2020, 13, 1443.
[http://dx.doi.org/10.3389/fnins.2019.01443] [PMID: 32063824]
[103]
Marino, B.L.B.; de Souza, L.R.; Sousa, K.P.A.; Ferreira, J.V.; Padilha, E.C.; da Silva, C.H.T.P.; Taft, C.A.; Hage-Melim, L.I.S. Parkinson’s disease: A review from pathophysiology to treatment. Mini Rev. Med. Chem., 2020, 20(9), 754-767.
[http://dx.doi.org/10.2174/1389557519666191104110908] [PMID: 31686637]
[104]
Tóth, A.; Antal, Z.; Bereczki, D.; Sperlágh, B. Purinergic Signalling in Parkinson’s Disease: A multi-target system to combat neurodegeneration. Neurochem. Res., 2019, 44(10), 2413-2422.
[http://dx.doi.org/10.1007/s11064-019-02798-1] [PMID: 31054067]
[105]
Sasaki, N.A.; Sonnet, P. A novel multi-target strategy to attenuate the progression of Parkinson’s disease by diamine hybrid AGE/ALE inhibitor. Future Med. Chem., 2021, 13(24), 2185-2200.
[http://dx.doi.org/10.4155/fmc-2021-0217] [PMID: 34634921]
[106]
Li, L.; Qiu, H.; Liu, M.; Cai, Y. A network pharmacology-based study of the molecular mechanisms of Shaoyao-Gancao Decoction in treating Parkinson’s Disease. Interdiscip. Sci., 2020, 12(2), 131-144.
[http://dx.doi.org/10.1007/s12539-020-00359-7] [PMID: 32006382]
[107]
Maqbool, M.; Rajvansh, R.; Srividya, K.; Hoda, N. Deciphering the robustness of pyrazolo-pyridine carboxylate core structure-based compounds for inhibiting α-synuclein in transgenic C. elegans model of Synucleinopathy. Bioorg. Med. Chem., 2020, 28(17), 115640.
[http://dx.doi.org/10.1016/j.bmc.2020.115640] [PMID: 32773095]
[108]
Anastassova, N.; Aluani, D.; Kostadinov, A.; Rangelov, M.; Todorova, N.; Hristova-Avakumova, N.; Argirova, M.; Lumov, N.; Kondeva-Burdina, M.; Tzankova, V.; Yancheva, D. Evaluation of the combined activity of benzimidazole arylhydrazones as new anti-Parkinsonian agents: monoamine oxidase-B inhibition, neuroprotection and oxidative stress modulation. Neural Regen. Res., 2021, 16(11), 2299-2309.
[http://dx.doi.org/10.4103/1673-5374.309843] [PMID: 33818516]
[109]
Elsherbeny, M.H.; Kim, J.; Gouda, N.A.; Gotina, L.; Cho, J.; Pae, A.N.; Lee, K.; Park, K.D.; Elkamhawy, A.; Roh, E.J. Highly potent, selective, and competitive indole-based MAO-B inhibitors protect PC12 cells against 6-Hydroxydopamine- and Rotenone-induced oxidative stress. Antioxidants, 2021, 10(10), 1641.
[http://dx.doi.org/10.3390/antiox10101641] [PMID: 34679775]
[110]
Elkamhawy, A.; Woo, J.; Gouda, N.A.; Kim, J.; Nada, H.; Roh, E.J.; Park, K.D.; Cho, J.; Lee, K. Melatonin analogues potently inhibit MAO-B and protect PC12 cells against oxidative stress. Antioxidants, 2021, 10(10), 1604.
[http://dx.doi.org/10.3390/antiox10101604] [PMID: 34679739]
[111]
Załuski, M.; Schabikowski, J.; Schlenk, M.; Olejarz-Maciej, A.; Kubas, B.; Karcz, T.; Kuder, K.; Latacz, G.; Zygmunt, M.; Synak, D.; Hinz, S.; Müller, C.E.; Kieć-Kononowicz, K. Novel multi-target directed ligands based on annelated xanthine scaffold with aromatic substituents acting on adenosine receptor and monoamine oxidase B. Synthesis, in vitro and in silico studies. Bioorg. Med. Chem., 2019, 27(7), 1195-1210.
[http://dx.doi.org/10.1016/j.bmc.2019.02.004] [PMID: 30808606]
[112]
Seong, S.H.; Paudel, P.; Choi, J.W.; Ahn, D.H.; Nam, T.J.; Jung, H.A.; Choi, J.S. Probing multi-target action of phlorotannins as new monoamine oxidase inhibitors and dopaminergic receptor modulators with the potential for treatment of neuronal disorders. Mar. Drugs, 2019, 17(6), 377.
[http://dx.doi.org/10.3390/md17060377] [PMID: 31238535]
[113]
Li, F.; Hatano, T.; Hattori, N. Systematic analysis of the molecular mechanisms mediated by coffee in Parkinson’s disease based on network pharmacology approach. J. Funct. Foods, 2021, 87, 104764.
[http://dx.doi.org/10.1016/j.jff.2021.104764]

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