title: A 2-Substituted 8-Hydroxyquinoline Stimulates Neural Stem Cell Proliferation by Modulating ROS Signalling.
abstract: Eight-hydroxyquinolines (8HQs) are a class of compounds that have been identified as potential therapeutics for a number of neurodegenerative diseases. Understanding the influence of structural modifications to the 8HQ scaffold on cellular behaviour will aid the identification of compounds that might be effective in treating dementias. In this study, we describe the action of 2-[(dimethylamino)methyl]-8-hydroxyquinoline (DMAMQ) on adult murine neural stem cells (NSCs) cultured in vitro. Treatment of NSCs with DMAMQ resulted in enhanced self-renewal and increased neurite outgrowth. Concurrent with the positive growth effects was an increase in intracellular reactive oxygen species, with the growth being inhibited by inactivation of the NADPH oxidase (Nox) enzyme family. Our results indicate that DMAMQ can stimulate neurogenesis via the Nox signalling pathway, which may provide therapeutic benefit in treating dementias of various types by replenishing neurones using the brain's own reserves. The narrow concentration range over which these effects were observed, however, suggests that there may exist only a small therapeutic window for neuro-regenerative applications.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Victoria, 3010, Australia. chaigh@unimelb.edu.au.
authors.forename: Cathryn L
authors.identifier: http://orcid.org/0000-0001-7591-1149
authors.initials: CL
authors.lastname: Haigh
authors.affiliation: Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia.
authors.forename: Carolin
authors.initials: C
authors.lastname: Tumpach
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Victoria, 3010, Australia.
authors.forename: Steven J
authors.identifier: http://orcid.org/0000-0002-5245-6611
authors.initials: SJ
authors.lastname: Collins
authors.affiliation: Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. sdrew@unimelb.edu.au.
authors.forename: Simon C
authors.identifier: http://orcid.org/0000-0002-1459-9865
authors.initials: SC
authors.lastname: Drew
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005434:Flow Cytometry; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D019255:NADPH Oxidases / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D015125:Oxyquinoline / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D019394:Ki-67 Antigen; D017382:Reactive Oxygen Species; D015125:Oxyquinoline; D019255:NADPH Oxidases
keywords: 2-[(dimethylamino)methyl]-8-hydroxyquinoline; 8-hydroxyquinoline; DMAMQ; NADPH oxidase; Neural stem cells; Neurosphere; PBT2; Proliferation; Reactive oxygen species