Genetic Susceptibility Model of Parkinson's Disease Resulting from Exposure of DJ-1 Deficient Mice to MPTP: Evaluation of Neuroprotection by Ubisol-Q10

被引：15

作者：

Muthukumaran, Krithika ^{[1
]}

Smith, Jessica ^{[1
]}

Jasra, Harshil ^{[1
]}

Sikorska, Marianna ^{[2
]}

Sandhu, Jagdeep K. ^{[2
]}

Cohen, Jerome ^{[1
]}

Lopatin, Daniel ^{[1
]}

Pandey, Siyaram ^{[1
]}

机构：

[1] Univ Windsor, Windsor, ON N9B 3P4, Canada

[2] Natl Res Council Canada, Human Hlth Therapeut Portfolio, Ottawa, ON, Canada

来源：

JOURNAL OF PARKINSONS DISEASE | 2014年 / 4卷 / 03期

基金：

加拿大自然科学与工程研究理事会;

关键词：

PD; DJ-1; MPTP; genetic susceptibility; coenzyme Q(10); mitochondrial dysfunction; WATER-SOLUBLE FORMULATION; OXIDATIVE STRESS; COENZYME Q(10); DJ-1-DEFICIENT MICE; NEURODEGENERATION; MITOCHONDRIA;

D O I：

10.3233/JPD-140368

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Introduction: 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 CoQ(10) (Ubisol-Q(10)) 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-Q(10)). Methods: Transgenic mice with DJ-1 deficiency (DJ-1/PARK7) were given either water or Ubisol-Q(10) 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- Q(10) 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- Q(10) significantly offset the neurotoxicity and ameliorated motor dysfunction, otherwise correlated with the MPTP injury. Conclusion: Ubisol- Q(10) protects against MPTP-induced neurodegeneration and motor dysfunction in DJ-1 deficient mice. Ubisol-Q(10) might be a treatment prospect for people genetically predisposed to PD as well as with sporadic PD.

引用

页码：523 / 530

页数：8

共 20 条

[1] DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase [J].