dc.creator | Chakraborty, Sudipta | |
dc.date.accessioned | 2020-08-21T21:10:22Z | |
dc.date.available | 2015-09-22 | |
dc.date.issued | 2015-03-26 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03152015-170233 | |
dc.identifier.uri | http://hdl.handle.net/1803/10795 | |
dc.description.abstract | Parkinson’s disease (PD) is a neurodegenerative, motor disorder that is characterized by selective dopaminergic cell loss in the substantia nigra pars compacta. About 10-20% of PD cases have genetic causes; nonetheless, the idiopathic nature of the majority of PD cases calls for the contribution of environmental factors in its etiology. One such factor is the essential trace element manganese (Mn); excessive exposure can result in “manganism,” which shares similarities with both PD symptomatology and molecular signatures. This overlap warrants investigation into whether a particular genetic risk factor increases susceptibility of DAergic neurons to environmental risk factors. Using the Caenorhabditis elegans (C. elegans) model system, loss of two genes associated with an early-onset, autosomal recessive form of PD, pdr-1/parkin and djr-1/dj-1, results in enhanced Mn accumulation and oxidative stress that can be rescued by the expression of another PD-associated protein known as α-Syn (alpha-synuclein), a protein found aggregated in some PD cases. Moreover, the loss of pdr-1/parkin results in increased mRNA expression of a Mn export gene known as ferroportin (fpn-1). As overexpression of this exporter can rescue pdr-1/parkin mutant phenotypes, these studies support the role of abnormal metal homeostasis as a consequence of genetic mutations associated with early-onset PD. | |
dc.format.mimetype | application/pdf | |
dc.subject | Parkinsons disease | |
dc.subject | manganese | |
dc.subject | neurotoxicology | |
dc.subject | C. elegans | |
dc.subject | parkin | |
dc.subject | pink1 | |
dc.subject | dj1 | |
dc.subject | ferroportin | |
dc.subject | DMT1 | |
dc.subject | oxidative stress | |
dc.title | Gene-Environment Interactions Between Manganese Toxicity and Early-Onset Parkinson's Disease Genes | |
dc.type | dissertation | |
dc.contributor.committeeMember | Michael Aschner | |
dc.contributor.committeeMember | Aaron Bowman | |
dc.contributor.committeeMember | Keith Erikson | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Neuroscience | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2015-09-22 | |
local.embargo.lift | 2015-09-22 | |
dc.contributor.committeeChair | William Valentine | |