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Review

Multifunctional neuroprotective drugs targeting monoamine oxidase inhibition, iron chelation, adenosine receptors, and cholinergic and glutamatergic action for neurodegenerative diseases

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Pages 873-886 | Published online: 21 Jul 2006

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Cornelis J Van der Schyf. (2015) Rational drug discovery design approaches for treating Parkinson’s disease. Expert Opinion on Drug Discovery 10:7, pages 713-741.
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Werner J Geldenhuys & Cornelis J Van der Schyf. (2013) Designing drugs with multi-target activity: the next step in the treatment of neurodegenerative disorders. Expert Opinion on Drug Discovery 8:2, pages 115-129.
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Cornelis J Van der Schyf. (2011) The use of multi-target drugs in the treatment of neurodegenerative diseases. Expert Review of Clinical Pharmacology 4:3, pages 293-298.
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Antoni Camins, Francesc Xavier Sureda, Felix Junyent, Ester Verdaguer, Jaume Folch, Carlos Beas-Zarate & Merce Pallas. (2010) An overview of investigational antiapoptotic drugs with potential application for the treatment of neurodegenerative disorders. Expert Opinion on Investigational Drugs 19:5, pages 587-604.
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Articles from other publishers (49)

Sudhir Raghavan, David S. Baskin & Martyn A. Sharpe. 2021. Encyclopedia of Biological Chemistry III. Encyclopedia of Biological Chemistry III 542 560 .
Shoaib Manzoor & Nasimul Hoda. (2020) A comprehensive review of monoamine oxidase inhibitors as Anti-Alzheimer’s disease agents: A review. European Journal of Medicinal Chemistry 206, pages 112787.
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Md. Sahab Uddin, Md. Tanvir Kabir, Md. Habibur Rahman, Md. Abdul Alim, Md. Motiar Rahman, Anurag Khatkar, Abdullah Al Mamun, Abdur Rauf, Bijo Mathew & Ghulam Md. Ashraf. (2020) Exploring the Multifunctional Neuroprotective Promise of Rasagiline Derivatives for Multi-Dysfunctional Alzheimer’s Disease. Current Pharmaceutical Design 26:37, pages 4690-4698.
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Bijo Mathew, Della G. T. Parambi, Githa E. Mathew, Md. Sahab Uddin, Sini T. Inasu, Hoon Kim, Akash Marathakam, Mazhuvancherry Kesavan Unnikrishnan & Simone Carradori. (2019) Emerging therapeutic potentials of dual‐acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Archiv der Pharmazie 352:11, pages 1900177.
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Siew L. Cheong, Stephanie Federico, Giampiero Spalluto, Karl-Norbert Klotz & Giorgia Pastorin. (2019) The current status of pharmacotherapy for the treatment of Parkinson’s disease: transition from single-target to multitarget therapy. Drug Discovery Today 24:9, pages 1769-1783.
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Idalet Engelbrecht, Jacobus P. Petzer & Anél Petzer. (2019) Evaluation of Selected Natural Compounds as Dual Inhibitors of Catechol-O-Methyltransferase and Monoamine Oxidase. Central Nervous System Agents in Medicinal Chemistry 19:2, pages 133-145.
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Yixiang Xu, Jian Zhang, Huan Wang, Fei Mao, Keting Bao, Wenwen Liu, Jin Zhu, Xiaokang Li, Haiyan Zhang & Jian Li. (2018) Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer’s Disease Agents. ACS Chemical Neuroscience 10:1, pages 482-496.
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Genevieve Z. Steiner, Alan Bensoussan, Jianxun Liu, Mark I. Hohenberg & Dennis H. Chang. (2018) Study protocol for a randomised, double-blind, placebo-controlled 12-week pilot phase II trial of Sailuotong (SLT) for cognitive function in older adults with mild cognitive impairment. Trials 19:1.
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Moussa B. H. Youdim. (2018) Monoamine oxidase inhibitors, and iron chelators in depressive illness and neurodegenerative diseases. Journal of Neural Transmission 125:11, pages 1719-1733.
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Tamar Amit, Orit Bar-Am, Danit Mechlovich, Lana Kupershmidt, Moussa B.H. Youdim & Orly Weinreb. (2017) The novel multitarget iron chelating and propargylamine drug M30 affects APP regulation and processing activities in Alzheimer's disease models. Neuropharmacology 123, pages 359-367.
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Chun-Li Xia, Ning Wang, Qian-Liang Guo, Zhen-Quan Liu, Jia-Qiang Wu, Shi-Liang Huang, Tian-Miao Ou, Jia-Heng Tan, Hong-Gen Wang, Ding Li & Zhi-Shu Huang. (2017) Design, synthesis and evaluation of 2-arylethenyl- N -methylquinolinium derivatives as effective multifunctional agents for Alzheimer's disease treatment. European Journal of Medicinal Chemistry 130, pages 139-153.
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Wei Liu, Ming Lang, Moussa B.H. Youdim, Tamar Amit, Yewei Sun, Zaijun Zhang, Yuqiang Wang & Orly Weinreb. (2016) Design, synthesis and evaluation of novel dual monoamine-cholinesterase inhibitors as potential treatment for Alzheimer’s disease. Neuropharmacology 109, pages 376-385.
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Rati K. P. Tripathi, Gopal K. Rai & Senthil R. Ayyannan. (2016) Exploration of a Library of 3,4-(Methylenedioxy)aniline-Derived Semicarbazones as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase: Design, Synthesis, and Evaluation. ChemMedChem 11:11, pages 1145-1160.
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Genevieve Z. Steiner, Alan Yeung, Jian-Xun Liu, David A. Camfield, Frances M. de Blasio, Andrew Pipingas, Andrew B. Scholey, Con Stough & Dennis H. Chang. (2016) The effect of Sailuotong (SLT) on neurocognitive and cardiovascular function in healthy adults: a randomised, double-blind, placebo controlled crossover pilot trial. BMC Complementary and Alternative Medicine 16:1.
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Mithilesh Kumar Jha, Shinrye Lee, Dong Ho Park, Hyun Kook, Keun-Gyu Park, In-Kyu Lee & Kyoungho Suk. (2015) Diverse functional roles of lipocalin-2 in the central nervous system. Neuroscience & Biobehavioral Reviews 49, pages 135-156.
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Beom-Cheol Kim, Seung-Hwan Lee, Mi Jang, Moo-Ho Won & Jeong Ho Park. (2015) ( S )-Allyl Cysteine Derivatives as a New-type Cholinesterase Inhibitor . Bulletin of the Korean Chemical Society 36:1, pages 52-58.
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Werner J. Geldenhuys, Akiko Kochi, Li Lin, Vijaykumar Sutariya, Dean E. Dluzen, Cornelis J. Van der Schyf & Mi Hee Lim. (2014) Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease. ChemBioChem 15:11, pages 1591-1598.
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ZHIYOU CAI. (2014) Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review). Molecular Medicine Reports 9:5, pages 1533-1541.
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Alejandro Romero, Eva Ramos, Cristóbal de Los Ríos, Javier Egea, Javier del Pino & Russel J. Reiter. (2014) A review of metal-catalyzed molecular damage: protection by melatonin. Journal of Pineal Research 56:4, pages 343-370.
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Elizabeth C. M. de Lange. 2014. Drug Delivery to the Brain. Drug Delivery to the Brain 591 634 .
Orly Weinreb, Silvia Mandel, Moussa B.H. Youdim & Tamar Amit. (2013) Targeting dysregulation of brain iron homeostasis in Parkinson's disease by iron chelators. Free Radical Biology and Medicine 62, pages 52-64.
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Florian Nachon, Eugénie Carletti, Cyril Ronco, Marie Trovaslet, Yvain Nicolet, Ludovic Jean & Pierre-Yves Renard. (2013) Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer's drugs targeting acetyl- and butyryl-cholinesterase. Biochemical Journal 453:3, pages 393-399.
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Irene Bolea, Alejandro Gella & Mercedes Unzeta. (2012) Propargylamine-derived multitarget-directed ligands: fighting Alzheimer’s disease with monoamine oxidase inhibitors. Journal of Neural Transmission 120:6, pages 893-902.
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Claudia Funke, Susanne A. Schneider, Daniela Berg & Douglas B. Kell. (2013) Genetics and iron in the systems biology of Parkinson’s disease and some related disorders. Neurochemistry International 62:5, pages 637-652.
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Cristina Rodríguez-Rodríguez, Maria Telpoukhovskaia & Chris Orvig. (2012) The art of building multifunctional metal-binding agents from basic molecular scaffolds for the potential application in neurodegenerative diseases. Coordination Chemistry Reviews 256:19-20, pages 2308-2332.
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Jacques Joubert, Werner J. Geldenhuys, Cornelis J. Van der Schyf, Douglas W. Oliver, Hendrik Gert Kruger, Thavendran Govender & Sarel F. Malan. (2012) Polycyclic Cage Structures as Lipophilic Scaffolds for Neuroactive Drugs. ChemMedChem 7:3, pages 375-384.
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Yuming Zhao, Juan Dou, Jialie Luo, Wenming Li, Hugh H.N. Chan, Wei Cui, Huan Zhang, Renwen Han, Paul R. Carlier, Xuejun Zhang & Yifan Han. (2011) Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets. Brain Research 1421, pages 100-109.
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David A. Camfield, Lauren Owen, Andrew B. Scholey, Andrew Pipingas & Con Stough. (2011) Dairy constituents and neurocognitive health in ageing. British Journal of Nutrition 106:2, pages 159-174.
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Orly Weinreb, Silvia Mandel, Orit Bar-Am & Tamar Amit. (2011) Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety as novel pluripotential therapeutic agents for Alzheimer’s disease: a tribute to Moussa Youdim. Journal of Neural Transmission 118:3, pages 479-492.
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P. Matthew Joyner & Robert H. Cichewicz. (2011) Bringing natural products into the fold – exploring the therapeutic lead potential of secondary metabolites for the treatment of protein-misfolding-related neurodegenerative diseases. Nat. Prod. Rep. 28:1, pages 26-47.
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Orly Weinreb, Tamar Amit, Orit Bar-Am & Moussa B.H. Youdim. 2011. Monoamine Oxidase and their Inhibitors. Monoamine Oxidase and their Inhibitors 191 215 .
Moussa B. H. Youdim. (2010) Why Do We Need Multifunctional Neuroprotective and Neurorestorative Drugs for Parkinson's and Alzheimer's Diseases as Disease Modifying Agents. Experimental Neurobiology 19:1, pages 1.
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Werner J. Geldenhuys, Lois-May Bezuidenhout & Dean E. Dluzen. (2009) Effects of a novel dopamine uptake inhibitor upon extracellular dopamine from superfused murine striatal tissue. European Journal of Pharmacology 619:1-3, pages 38-43.
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P. Szaniszlo, P. German, G. Hajas, D. N. Saenz, M. Kruzel & I. Boldogh. (2009) New insights into clinical trial for colostrinin™ in Alzheimer’s disease. The Journal of Nutrition, Health and Aging 13:3, pages 235-241.
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Peter Szaniszlo, Peter German, Gyorgy Hajas, David N. Saenz, Mitchell W. Woodberry, Marian L. Kruzel & Istvan Boldogh. (2009) Effects of Colostrinin™ on gene expression-transcriptomal network analysis. International Immunopharmacology 9:2, pages 181-193.
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Cornells J. Schyf & Werner J. Geldenhuys. (2009) Polycyclic compounds: Ideal drug scaffolds for the design of multiple mechanism drugs?. Neurotherapeutics 6:1, pages 175-186.
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Jerry J. Buccafusco. (2009) Multifunctional receptor-directed drugs for disorders of the central nervous system. Neurotherapeutics 6:1, pages 4-13.
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Orly Weinreb, Silvia Mandel, Orit Bar-Am, Merav Yogev-Falach, Yael Avramovich-Tirosh, Tamar Amit & Moussa B. H. Youdim. (2009) Multifunctional neuroprotective derivatives of rasagiline as anti-alzheimer’s disease drugs. Neurotherapeutics 6:1, pages 163-174.
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Trevor W. Stone, Stefania Ceruti & Mariapia P. Abbracchio. 2009. Adenosine Receptors in Health and Disease. Adenosine Receptors in Health and Disease 535 587 .
Silvia A. Mandel, Tamar Amit, Orly Weinreb, Lydia Reznichenko & Moussa B. H. Youdim. (2008) Simultaneous Manipulation of Multiple Brain Targets by Green Tea Catechins: A Potential Neuroprotective Strategy for Alzheimer and Parkinson Diseases. CNS Neuroscience & Therapeutics 14:4, pages 352-365.
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Silvia A. Mandel, Tamar Amit, Limor Kalfon, Lydia Reznichenko & MoussaBH Youdim. (2008) Targeting Multiple Neurodegenerative Diseases Etiologies with Multimodal-Acting Green Tea Catechins. The Journal of Nutrition 138:8, pages 1578S-1583S.
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Jiukuan Hao, Alexander Mdzinarishvili, Thomas J. Abbruscato, Jochen Klein, Werner J. Geldenhuys, Cornelis J. Van der Schyf & Ulrich Bickel. (2008) Neuroprotection in mice by NGP1-01 after transient focal brain ischemia. Brain Research 1196, pages 113-120.
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Tomoyuki Kanda & Akihisa Mori. (2008) Recent and potential drug candidates for treatment of Parkinson's disease. Folia Pharmacologica Japonica 131:4, pages 275-280.
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Walter S. Jellish, Xin Zhang, Kenneth E. Langen, Matthew S. Spector, Michael T. Scalfani & Fletcher A. White. (2008) Intrathecal Magnesium Sulfate Administration at the Time of Experimental Ischemia Improves Neurological Functioning by Reducing Acute and Delayed Loss of Motor Neurons in the Spinal Cord. Anesthesiology 108:1, pages 78-86.
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Cornelis J Van der SchyfWerner J GeldenhuysMoussa BH Youdim. (2007) Multifunctional neuroprotective–neurorescue drugs for Parkinson’s disease. Future Neurology 2:4, pages 411-423.
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Roberto CappaiKevin J Barnham. (2007) Molecular determinants of Alzheimer’s disease Aβ peptide neurotoxicity. Future Neurology 2:4, pages 397-409.
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Julie A. Gaasch, Paul R. Lockman, Werner J. Geldenhuys, David D. Allen & Cornelis J. Van der Schyf. (2007) Brain Iron Toxicity: Differential Responses of Astrocytes, Neurons, and Endothelial Cells. Neurochemical Research 32:7, pages 1196-1208.
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Moussa B. H. Youdim & Cornelis J. Van der Schyf. (2007) Magic bullets or novel multimodal drugs with various CNS targets for Parkinson's disease?. Nature Reviews Drug Discovery 6:6, pages 500-500.
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Moussa B.H. Youdim, Werner J. Geldenhuys & Cornelis J. Van der Schyf. (2007) Why should we use multifunctional neuroprotective and neurorestorative drugs for Parkinson's disease?. Parkinsonism & Related Disorders 13, pages S281-S291.
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