title: Effects of NK-4 in a transgenic mouse model of Alzheimer's disease.
abstract: Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and molecules that can prevent pathways of Aβ toxicity may be potential therapeutic agents for treatment of AD. We have previously reported that NK-4, a cyanine photosensitizing dye, displays neurotrophic and antioxidant activities. In this study, we report the effects of NK-4 on the toxicity of Aβ and on cognitive function and Aβ concentration in a transgenic mouse model of AD (Tg2576). In vitro, NK-4 effectively protected neuronal cells from toxicity induced by Aβ. In addition, it displayed profound inhibitory activities on Aβ fibril formation. In vivo, Tg2576 mice received an intraperitoneal injection at 100 or 500 µg/kg of NK-4 once a day, five times a week for 9 months. Administration of NK-4 to the mice attenuated impairment of recognition memory, associative memory, and learning ability, as assessed by a novel object recognition test, a passive avoidance test, and a water maze test, respectively. NK-4 decreased the brain Aβ concentration while increasing the plasma amyloid level in a dose-dependent manner. NK-4 also improved memory impairments of ICR mice induced by direct intracerebroventricular administration of Aβ. These lines of evidence suggest that NK-4 may affect multiple pathways of amyloid pathogenesis and could be useful for treatment of AD.
authors.affiliation: Research Center, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan. htmohta@hayashibara.co.jp
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ohta
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Arai
authors.forename: Kenji
authors.initials: K
authors.lastname: Akita
authors.forename: Tsunetaka
authors.initials: T
authors.lastname: Ohta
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fukuda
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D000818:Animals; D002232:Carbocyanines; D002491:Central Nervous System Agents / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D016716:PC12 Cells; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013550:Swimming / Q000502:physiology / Q000523:psychology
chemical_list: C572048:4,4'-(3-(2-(1-ethyl-4(1H)-quinolylidene)ethylidene)propenylene)bis(1-ethylquinolinium); D002232:Carbocyanines; D002491:Central Nervous System Agents; D017319:Photosensitizing Agents; D011804:Quinolines