Multi-target, neuroprotective and neurorestorative M30 improves cognitive impairment and reduces Alzheimer's-like neuropathology and age-related alterations in mice.

Abstract

Based on a multimodal drug design strategy for age-related neurodegenerative diseases, we have synthesized a multifunctional nontoxic, brain-permeable iron-chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase-B inhibitor, rasagiline and the antioxidant-iron chelator moiety of the 8-hydroxyquinoline derivative of the iron chelator, VK28. In the present short overview, we describe the neuroprotective and the neurorestorative activity of M30, acting against multiple brain targets, including regulation on amyloid β, neurogenesis, and activation of hypoxia inducible factor signaling pathways. The diverse pharmacological properties and several pathological targets of M30 make this drug potential valuable for therapeutic strategy of Alzheimer's-like neuropathology and aging.

• Authors: Lana Kupershmidt, Tamar Amit, Orit Bar-Am, Orly Weinreb, Moussa B H Youdim
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 46 Issue 1 Pg. 217-20 (Aug 2012) ISSN: 1559-1182 [Electronic] United States
• PMID: 22847630 (Publication Type: Journal Article)

Chemical References

• 5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline
• Hydroxyquinolines
• Neuroprotective Agents

Topics

• Aging (drug effects, pathology)
• Alzheimer Disease (drug therapy, pathology)
• Amyloidosis (drug therapy, pathology)
• Animals
• Brain (drug effects, pathology)
• Cognition Disorders (drug therapy, pathology)
• Hydroxyquinolines (chemistry, pharmacology, therapeutic use)
• Mice
• Neuroprotective Agents (pharmacology, therapeutic use)