1.
Therapeutic strategies in Friedreich's ataxia.
Richardson, TE, Kelly, HN, Yu, AE, Simpkins, JW
Brain research. 2013;:91-7
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Abstract
First established as a diagnosis by Nikolaus Friedreich in 1863, Friedreich's ataxia (FA) is an autosomal recessive progressive neurodegenerative disorder cause by a trinucleotide repeat expansion. FA begins with the functional absence of the FXN gene product frataxin, a protein whose exact function still remains unknown. This absence results in impaired intracellular antioxidant defenses, dysregulation of iron-sulfur cluster proteins, depression of aerobic electron transport chain respiration, massive mitochondrial dysfunction, and ultimately cell death in the brain, spinal cord and heart. Herein, we review the molecular and cellular pathogenesis leading to widespread organ system dysfunction, as well as current therapeutic research aimed at preventing the debilitating effects of frataxin loss and preventing the signs and symptoms associated of FA. We also discuss the ongoing treatment strategies employed by our laboratory to prevent mitochondrial damage using synergistic effects of 17β-estradiol and methylene blue, previously shown by our group and others to have protective effects in human FA fibroblasts. This article is part of a Special Issue entitled Hormone Therapy.
2.
Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety as novel pluripotential therapeutic agents for Alzheimer's disease: a tribute to Moussa Youdim.
Weinreb, O, Mandel, S, Bar-Am, O, Amit, T
Journal of neural transmission (Vienna, Austria : 1996). 2011;(3):479-92
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.