Journal
NEURODEGENERATIVE DISEASES
Volume 10, Issue 1-4, Pages 112-115Publisher
KARGER
DOI: 10.1159/000332597
Keywords
Alzheimer's disease; Amyotrophic lateral sclerosis; Neuroprotection; Hypoxia-inducible factor; Iron chelators; M30; HLA20
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Our novel multimodal brain-permeable iron-chelating compounds M30 and HLA20 were demonstrated to possess neuroprotective/neurorescue activities in vitro and in vivo against several insults applicable to various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Neuroprotection by iron chelators has been widely recognized with respect to their ability to prevent reactive oxygen species generation in the Fenton reaction by sequestering redox-active iron. An additional neuroprotective mechanism of iron-chelating compounds is associated with their ability to regulate the transcriptional activator hypoxia-inducible factor 1 (HIF-1). HIF-1 is a 'master switch' being an important physiological response mechanism, likely enhancing neuroprotective compensatory pathways involved in many physiological processes within the brain. This mini-review will discuss the multifunctional mechanisms of action of the drugs, M30 and HLA20 in preclinical models of neurodegeneration with a specific emphasis on their ability to activate the HIF-1 signal transduction pathway. Copyright (C) 2011 S. Karger AG, Basel
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