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.