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Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety as novel pluripotential therapeutic agents for Alzheimer’s disease: a tribute to Moussa Youdim

  • Basic Neurosciences, Genetics and Immunology - Review Article
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Abstract

It is for these authors a great privilege to dedicate this review article to Moussa Youdim, who is one of the most imperative pharmacologists and pioneer investigators in the search and development of novel therapeutics for neurodegenerative diseases. 40 years ago, Moussa Youdim has started studying brain iron, catecholamine receptor and monoamine oxidase (MAO)-A and -B functions. Although Moussa Youdim succeeded in exploring the novel anti-Parkinsonian, selective MAO-B inhibitor drug, rasagiline (Azilect, Teva Pharmaceutical Co.), he did not stop searching for superior therapeutic approaches for neurodegenerative disorders. To date, Moussa Youdim and his research group are designing and synthesizing pluripotential drug candidates possessing diverse pharmacological properties that can act on multiple targets and pathological features ascribed to Parkinson’s disease, Alzheimer’s disease (AD) and amyotrophic lateral sclerosis. One such example is the multimodal non-toxic, brain-permeable iron-chelating compound, M30 (5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline), which amalgamates the propargyl moiety of rasagiline with the backbone of the potent iron chelator, VK28. This review discusses the multiple effects of several leading compounds of this series, concerning their neuroprotective/neurorestorative molecular mechanisms in vivo and in vitro, with a special focus on the pathological features ascribed to AD, including antioxidant and iron chelating activities, regulation of amyloid precursor protein and amyloid β peptide expression processing, activation of pro-survival signaling pathways and regulation of cell cycle and neurite outgrowth.

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Acknowledgments

The authors gratefully acknowledge the support of the Alzheimer’s Drug Discovery Foundation (ADDF), the Alzheimer’s Association (Chicago, USA), and the Technion-Research and Development and Rappaport Family Research Institute, Technion-Israel Institute of Technology (Haifa, Israel).

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  1. Eve Topf Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute, Technion-Faculty of Medicine, P.O.B. 9697, 31096, Haifa, Israel

    Orly Weinreb, Silvia Mandel, Orit Bar-Am & Tamar Amit

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  1. Orly Weinreb
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  2. Silvia Mandel
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Correspondence to Orly Weinreb.

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Weinreb, O., Mandel, S., Bar-Am, O. et al. Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety as novel pluripotential therapeutic agents for Alzheimer’s disease: a tribute to Moussa Youdim. J Neural Transm 118, 479–492 (2011). https://doi.org/10.1007/s00702-011-0597-6

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