title: Pharmacological characterization of memoquin, a multi-target compound for the treatment of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by progressive loss of cognitive function, dementia and altered behavior. Over 30 million people worldwide suffer from AD and available therapies are still palliative rather than curative. Recently, Memoquin (MQ), a quinone-bearing polyamine compound, has emerged as a promising anti-AD lead candidate, mainly thanks to its multi-target profile. MQ acts as an acetylcholinesterase and β-secretase-1 inhibitor, and also possesses anti-amyloid and anti-oxidant properties. Despite this potential interest, in vivo behavioral studies with MQ have been limited. Here, we report on in vivo studies with MQ (acute and sub-chronic treatments; 7-15 mg/kg per os) carried out using two different mouse models: i) scopolamine- and ii) beta-amyloid peptide- (Aβ-) induced amnesia. Several aspects related to memory were examined using the T-maze, the Morris water maze, the novel object recognition, and the passive avoidance tasks. At the dose of 15 mg/kg, MQ was able to rescue all tested aspects of cognitive impairment including spatial, episodic, aversive, short and long-term memory in both scopolamine- and Aβ-induced amnesia models. Furthermore, when tested in primary cortical neurons, MQ was able to fully prevent the Aβ-induced neurotoxicity mediated by oxidative stress. The results support the effectiveness of MQ as a cognitive enhancer, and highlight the value of a multi-target strategy to address the complex nature of cognitive dysfunction in AD.
authors: Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy.
authors: Valeria
authors: V
authors: Capurro
authors: Perrine
authors: P
authors: Busquet
authors: Joao Pedro
authors: JP
authors: Lopes
authors: Rosalia
authors: R
authors: Bertorelli
authors: Glauco
authors: G
authors: Tarozzo
authors: Maria Laura
authors: ML
authors: Bolognesi
authors: Daniele
authors: D
authors: Piomelli
authors: Angelo
authors: A
authors: Reggiani
authors: Andrea
authors: A
authors: Cavalli
mesh_terms: D000473:Alkanes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005021:Ethylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats
chemical_list: D000473:Alkanes; D016229:Amyloid beta-Peptides; D005021:Ethylamines; D018696:Neuroprotective Agents; C544092:beta-amyloid peptide 1-42 (E22delta) click peptide; C521476:memoquin