title: Inhibition of stress induced premature senescence in presenilin-1 mutated cells with water soluble Coenzyme Q10.
abstract: A water-soluble formulation of CoQ10 (WS-CoQ10) was shown to stabilize mitochondria and prevent oxidative stress-induced neuronal death. Presenilin-1 (PS-1)-mutated Alzheimer's Disease (AD) fibroblasts (PSAF) were used for studying the effects of PS-1 mutation. PS-1 mutation correlated to increased reactive oxygen species (ROS) production and stress induced premature senescence (SIPS) in PSAF; WS-CoQ10 treatment decreased ROS generation, increased population doublings, and postponed SIPS. Treated PSAF had higher PCNA expression, and lower levels of MnSOD, p21, p16Ink4A, and Rb. WS-CoQ10 caused the resumption of autophagy in PSAF. Thus, WS-CoQ10 as inhibitor of SIPS and ameliorator of autophagy could be an effective prophylactic/therapeutic agent for AD.
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada.
authors.forename: Dennis
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada.
authors.forename: Kyle
authors.initials: K
authors.lastname: Stokes
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada.
authors.forename: Kevinjeet
authors.initials: K
authors.lastname: Mahngar
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada.
authors.forename: Danijela
authors.initials: D
authors.lastname: Domazet-Damjanov
authors.affiliation: Institute For Biological Sciences, NRC, Ottawa, ON, Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Sikorska
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada. Electronic address: spandey@uwindsor.ca.
authors.forename: Siyaram
authors.initials: S
authors.lastname: Pandey
mesh_terms: D000375:Aging; D000544:Alzheimer Disease; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008297:Male; D053764:Presenilin-1 / Q000172:deficiency*; D013312:Stress, Physiological; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism; D014815:Vitamins / Q000378:metabolism*
chemical_list: D053764:Presenilin-1; D014815:Vitamins; D014451:Ubiquinone; C024989:coenzyme Q10
keywords: Alzheimer's disease; Autophagy; Coenzyme Q(10); Mitochondria; Reactive oxygen species; Senescence