Abstract
Oxidative stress is thought to play a significant role in the development and progression of neurodegenerative diseases. Although it is currently considered a hallmark of such processes, the interweaving of a multitude of signaling cascades hinders complete understanding of the direct role of oxidative stress in neurodegeneration. In addition to its extensive use as an aging model, some researchers have turned to the invertebrate model Caenorhabditis elegans (C. elegans) in order to further investigate molecular mediators that either exacerbate or protect against reactive oxygen species (ROS)-mediated neurodegeneration. Due to their fully characterized genome and short life cycle, rapid generation of C. elegans genetic models can be useful to study upstream markers of oxidative stress within interconnected signaling pathways. This report will focus on the roles of C. elegans homologs for the oxidative stress-associated transcription factor Nrf2, as well as the autosomal recessive, early-onset Parkinson’s disease (PD)-associated proteins Parkin, DJ-1, and PINK1, in neurodegenerative processes.
Highlights
The prevalence of neurodegenerative disorders, such as Parkinson’s disease (PD), has been increasing at a disconcerting rate
It is important to recognize the limitations of the dyes and avoid erroneous interpretations; DCFH-DA probe cannot reliably measure intracellular H2O2 and other reactive oxygen species, but instead may be more appropriate in use as a redox indicator probe that responds to oxidative insult [47]
The utilization of a model system, such as C. elegans, allows for ease in high-throughput screening and unbiased forward genetics approaches, in addition to faster genetic studies investigating the role and/or interplay of specific genes associated with the disease
Summary
The prevalence of neurodegenerative disorders, such as Parkinson’s disease (PD), has been increasing at a disconcerting rate. The invertebrate C. elegans model provides several appealing advantages to investigate the connection between oxidative stress and DAergic neurodegeneration in PD While these nematodes do not possess a brain, they do contain all necessary genetic information encoding components of the DAergic pathway [7]. While originally conducted by microinjecting plasmids containing double-stranded RNA (dsRNA) specific to the target gene, other delivery methods include feeding worms bacteria expressing the dsRNA of interest [19] or soaking them in a dsRNA-containing solution [20] While this technique is limited in expression specificity (some cells, such as neurons, are resistant to RNAi), there are RNAi-sensitive strains that allow for more effective knockdown (e.g., rrf-3 and eri-1 backgrounds) [21]. BioResource Project of Japan (NBRP) and the C. elegans Gene Knockout Consortium (GKC) [23]
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