title: Genetic susceptibility model of Parkinson's disease resulting from exposure of DJ-1 deficient mice to MPTP: evaluation of neuroprotection by Ubisol-Q10.
abstract: BACKGROUND
  Parkinson's disease arises from a combination of environmental and genetic risk factors. At present neither the curative nor preventative therapies are available; hence, there is an urgent need to develop reliable animal models to facilitate their development. Water soluble nanomiceller formulation of CoQ10 (Ubisol-Q10) has shown neuroprotection against neurotoxin on human neuronal cells. We have combined the genetic deficiency of DJ-1/PARK7 mice with MPTP exposure and develop a genetic susceptibility model of PD and evaluated the neuroprotective efficacy of (Ubisol-Q10).
  
  
  METHODS
  Transgenic mice with DJ-1 deficiency (DJ-1/PARK7) were given either water or Ubisol-Q10 prophylactically at a dose of 6 mg/kg/day added directly to a drinking water for one month followed challenged with MPTP injections while keeping the same drinking water regiments. Four weeks after the last injection we evaluated neuroprotective efficacy of Ubisol-Q10 in DJ-1/MPTP model of PD using histochemical and behavioral readouts.
  
  
  RESULTS
  We confirmed genetic susceptibility to MPTP and showed that prophylactic oral treatment with Ubisol-Q10 significantly offset the neurotoxicity and ameliorated motor dysfunction, otherwise correlated with the MPTP injury.
  
  
  CONCLUSIONS
  Ubisol-Q10 protects against MPTP-induced neurodegeneration and motor dysfunction in DJ-1 deficient mice. Ubisol-Q10 might be a treatment prospect for people genetically predisposed to PD as well as with sporadic PD.
authors: Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada.
authors: Krithika
authors: K
authors: Muthukumaran
authors: Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada.
authors: Jessica
authors: J
authors: Smith
authors: Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada.
authors: Harshil
authors: H
authors: Jasra
authors: Translational Bioscience, Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, Ontario, ON, Canada.
authors: Marianna
authors: M
authors: Sikorska
authors: Translational Bioscience, Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, Ontario, ON, Canada.
authors: Jagdeep K
authors: JK
authors: Sandhu
authors: Psychology, University of Windsor, Windsor, ON, Canada.
authors: Jerome
authors: J
authors: Cohen
authors: Psychology, University of Windsor, Windsor, ON, Canada.
authors: Daniel
authors: D
authors: Lopatin
authors: Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada.
authors: Siyaram
authors: S
authors: Pandey
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D020267:MPTP Poisoning / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015513:Oncogene Proteins / Q000235:genetics*; D065842:Pars Compacta / Q000187:drug effects / Q000473:pathology; D054464:Peroxiredoxins / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D014451:Ubiquinone; D054464:Peroxiredoxins; D014446:Tyrosine 3-Monooxygenase; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; C024989:coenzyme Q10
keywords: DJ-1; MPTP; PD; coenzyme $Q_{10}$; genetic susceptibility; mitochondrial dysfunction