title: 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: Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Technion-Faculty of Medicine, P.O. Box 9697, Haifa 31096, Israel.
authors: Lana
authors: L
authors: Kupershmidt
authors: Tamar
authors: T
authors: Amit
authors: Orit
authors: O
authors: Bar-Am
authors: Orly
authors: O
authors: Weinreb
authors: Moussa B H
authors: MB
authors: Youdim
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D000686:Amyloidosis / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000473:pathology*; D006912:Hydroxyquinolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C517687:5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline; D006912:Hydroxyquinolines; D018696:Neuroprotective Agents