Modeling and Analyzing Cellular Defects Associated with Movement Disorders in Caenorhabditis Elegans

Download or read book Modeling and Analyzing Cellular Defects Associated with Movement Disorders in Caenorhabditis Elegans written by Chuan Xu and published by . This book was released on 2018 with total page 138 pages. Available in PDF, EPUB and Kindle. Book excerpt: As a powerful modern organism, Caenorhabditis elegans has been widely used to study pathologies behind movement disorders including Parkinson's disease (PD) and dystonia. PD is the second most common neurodegenerative disease, in which more than 90% of cases are idiopathic. The etiology of PD has long been thought to involve both genetic and environmental factors. The classical pathological hallmarks of PD are the progressive loss of dopaminergic neurons within the substantia nigra, accompanied by the accumulation of a-synuclein (a-syn) in the form of Lewy bodies. Here, we identified four compounds (cyclosporin A, meclofenoxate hydrochloride, sulfaphenazole, and choline) that can rescue mitochondrial phospholipid depletion induced neurodegeneration in C. elegans with a-syn expression in dopaminergic neurons. To examine putative epigenetically-regulated modifiers of a-syn induced dopaminergic neurodegeneration in C. elegans, we demonstrated a specific microRNA, mir-239, when mutated, showed a robust resistance to neurotoxicity resulted from a-syn. By functionally investigating a suite of expression-validated targets of mir-239 regulation via conditional knockdown using a dopaminergic neuron-specific RNAi-sensitive a-syn strain, we discerned a subset of downstream targets contributing to neuroprotection afforded by mir-239. These findings support the predictive nature of C. elegans in validating potential modifiers of a-syn neurotoxicity and discovering potential neuroprotective chemicals associated with PD. Human torsinA, encoded by the DYT1 gene, is an ER resident chaperone protein that has been identified to be responsible for a human movement disorder called early-onset torsion dystonia. Here we revealed that tor-2, the C. elegans homologue of human torsinA, was indicated as a possible regulator in the trafficking process of an AMPA receptor subunit, GLR-1; implying a possible connection between the glutamatergic transmission and the etiology of dystonia. The combined outcomes of these studies of movement disorders strongly support C. elegans is a very desirable model organism for the analysis of cell biology and genetic features associated with PD and dystonia.