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

Abstract

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.

Combined Ubisol-Q10 and Ashwagandha Root Extract Target Multiple Biochemical Mechanisms and Reduces Neurodegeneration in a Paraquat-Induced Rat Model of Parkinson’s Disease

“…Chronic PQ or MPTP exposure in rats or mice is known to cause impaired motor performance on the rotarod task [14,35,36,46]. As already discussed, we focused our analysis on comparing the groups' proportion of head-down positions as they walked on a slowly rotating (6 rpm), 5-cm cylinder (rotarod) (Figure 2).…”

“…When combined with PTS, doses of coenzyme-Q 10 were able to be reduced significantly to 6 mg/kg/day. Ubisol-Q 10 has been shown to target mitochondrial dysfunction and oxidative stress in in vitro and in vivo models of PD [14,[32][33][34][35]. Furthermore, Ubisol-Q 10 prevented oxidative-stress-induced premature senescence and resumed impaired autophagy in Alzheimer's Disease (AD) fibroblasts, while also improving memory and removing beta-amyloid plaques in a transgenic mouse model of AD [36][37][38].…”

Enriched Environmental Conditions Modify the Gut Microbiome Composition and Fecal Markers of Inflammation in Parkinson’s Disease

“…Environmental factors appeared to improve and worsen the pathology of PD (Klingelhoefer and Reichmann, 2015; Delamarre and Meissner, 2017; Erro et al, 2018; Hu et al, 2019). Several chemicals or pesticides such as MPTP (Muthukumaran et al, 2014), paraquat (Park et al, 2005; Barlow et al, 2007), rotenone (Betarbet et al, 2000), viral infections (Bhattacharjee and Lukiw, 2013), etc., exposure to which lead to neurodegenerative effects whilst enriched environmental (EE) conditions based on studies of animal models suggested that enrichment can promote neuronal activation, signaling and plasticity in various brain regions. Therefore, EE conditions could possibly exert neuroprotective effects on neurons and delay pathogenesis in PD (Jadavji et al, 2006; Nithianantharajah and Hannan, 2006; Kotloski and Sutula, 2015).…”

Impairment of Nrf2- and Nitrergic-Mediated Gastrointestinal Motility in an MPTP Mouse Model of Parkinson’s Disease

“…Due to the lack of proper treatment available for GI dysmotility among PD patients, it is essential to discover new therapies that allow us to improve not only motor symptoms, but also non-motor symptoms, including cognitive impairment and dysfunction of the autonomic nervous system, and thereby modulate disease progression. PD may be initiated and/or precipitated by environmental or endogenous toxins by a mechanism similar to that of MPTP in genetically predisposed individuals [27]. The MPTP model has been widely accepted as a PD model that shows parkinsonogenic effects [28, 29].…”