Oxidative Stress in Genetic Mouse Models of Parkinson’s Disease

Abstract

There is extensive evidence in Parkinson's disease of a link between oxidative stress and some of the monogenically inherited Parkinson's disease-associated genes. This paper focuses on the importance of this link and potential impact on neuronal function. Basic mechanisms of oxidative stress, the cellular antioxidant machinery, and the main sources of cellular oxidative stress are reviewed. Moreover, attention is given to the complex interaction between oxidative stress and other prominent pathogenic pathways in Parkinson's disease, such as mitochondrial dysfunction and neuroinflammation. Furthermore, an overview of the existing genetic mouse models of Parkinson's disease is given and the evidence of oxidative stress in these models highlighted. Taken into consideration the importance of ageing and environmental factors as a risk for developing Parkinson's disease, gene-environment interactions in genetically engineered mouse models of Parkinson's disease are also discussed, highlighting the role of oxidative damage in the interplay between genetic makeup, environmental stress, and ageing in Parkinson's disease.

CHIP Is an Essential Determinant of Neuronal Mitochondrial Stress Signaling

“…Other E3 ligase-deficient animals, such as Parkin KO mice, are neurologically intact. Surprisingly, even triple transgenic KO of PINK1, Parkin, and DJ1 fails to produce an overt phenotype (8,9,19,38,57). The motor phenotype and oxidative stress we observed in CHIP KO animals occur in the CNS of relatively young animals (PND35), suggesting that CHIP deficiency has a major impact early in life.…”

“…DIV, day in vitro; OGD, oxygen-glucose deprivation; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis. in physiology are accompanied by high levels of CNS protein oxidation and lipid peroxidation and decreased antioxidant responses, which are far more profound than those observed in PINK1, DJ1, or Parkin-deficient animals (42,57).…”

Inhibition of Neuronal Cell Mitochondrial Complex I with Rotenone Increases Lipid β-Oxidation, Supporting Acetyl-Coenzyme A Levels

“…In particular, the complex I inhibitory effects of rotenone have been tied to the onset of a parkinsonian phenotype in both animal models and human studies (2-4). Although much focus has been placed on oxida- tive stress and the role it may play in the pathogenesis of neurodegeneration in PD (9,(32)(33)(34), there is substantial evidence to suggest that mitochondrial dysfunction may also contribute to this process (35,36).…”

Antioxidant Activity of Oral Administration of Rosmarinus Officinalis Leaves Extract on Rat's Hippocampus which Exposed to 6-Hydroxydopamine

“…However, studies conducted over the last two decades have shown that cognitive impairments, including spatial working memory deficits, occur even in the early stage of PD when motor symptoms are barely observed (Hirano et al 2003;Varcin et al 2012). The motor symptoms of PD are more known than cognitive disabilities.…”