UC San Diego
Biomarkers of progression in mirroring models of Parkinson's disease
- Author(s): Han, Brent
- et al.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is pathologically characterized by loss of dopaminergic neurons and formation of Lewy bodies composed of a-synuclein aggregates in substantia nigra. Other than the rarely inherited autosomal forms, the causes of most cases of idiopathic PD are not known. Increasing numbers of study are implicating the role of mitochondria and oxidative stress in the pathogenesis of PD. The neuronal susceptibility in PD is multifactorial involving strong interactions between the environmental toxins and the genetic predisposition. Past studies have shown that herbicide paraquat can reproduce features of PD in animals. Also, over-expression of a-synuclein has been implicated in the generation of Lewy bodies in in vitro studies. In the present study, the effects of both paraquat and a-synuclein over-expression have been studied to observe the degree of mitochondrial dysfunction in mice. This was done by investigating the amplification efficiency of the 16-kilobase mitochondrial DNA using extended-long PCR and determining the mitochondrial complex I activity in differently treated group of mice. To support the role of oxidative stress in mouse models of PD, the protein carbonyl levels and superoxide dismutase activities were also measured. Lastly, to confirm the specificity of a-synuclein, the effect of b-synuclein has been investigated, which is highly homologous and a co- localized protein. Further study with increased number of samples would better elucidate whether the biomarkers investigated in this study could become more reliable measures in predicting the progression of PD