Studying Parkinson's disease using Caenorhabditis elegans models in microfluidic devices.

Abstract

Parkinson's disease (PD) is a progressive neurological disorder associated with the loss of dopaminergic neurons (DNs) in the substantia nigra and the widespread accumulation of α-synuclein (α-syn) protein, leading to motor impairments and eventual cognitive dysfunction. In-vitro cell cultures and in-vivo animal models have provided the opportunity to investigate the PD pathological hallmarks and identify different therapeutic compounds. However, PD pathogenesis and causes are still not well understood, and effective inhibitory drugs for PD are yet to be discovered. Biologically simple but pathologically relevant disease models and advanced screening technologies are needed to reveal the mechanisms underpinning protein aggregation and PD progression. For instance, Caenorhabditis elegans (C. elegans) offers many advantages for fundamental PD neurobehavioral studies including a simple, well-mapped, and accessible neuronal system, genetic homology to humans, body transparency and amenability to genetic manipulation. Several transgenic worm strains that exhibit multiple PD-related phenotypes have been developed to perform neuronal and behavioral assays and drug screening. However, in conventional worm-based assays, the commonly used techniques are equipment-intensive, slow and low in throughput. Over the past two decades, microfluidics technology has contributed significantly to automation and control of C. elegans assays. In this review, we focus on C. elegans PD models and the recent advancements in microfluidic platforms used for manipulation, handling and neurobehavioral screening of these models. Moreover, we highlight the potential of C. elegans to elucidate the in-vivo mechanisms of neuron-to-neuron protein transfer that may underlie spreading Lewy pathology in PD, and its suitability for in-vitro studies. Given the advantages of C. elegans and microfluidics technology, their integration has the potential to facilitate the investigation of disease pathology and discovery of potential chemical leads for PD.