title: Alpha-synuclein disrupted dopamine homeostasis leads to dopaminergic neuron degeneration in Caenorhabditis elegans.
abstract: Disruption of dopamine homeostasis may lead to dopaminergic neuron degeneration, a proposed explanation for the specific vulnerability of dopaminergic neurons in Parkinson's disease. While expression of human alpha-synuclein in C. elegans results in dopaminergic neuron degeneration, the effects of alpha-synuclein on dopamine homeostasis and its contribution to dopaminergic neuron degeneration in C. elegans have not been reported. Here, we examined the effects of alpha-synuclein overexpression on worm dopamine homeostasis. We found that alpha-synuclein expression results in upregulation of dopamine synthesis and content, and redistribution of dopaminergic synaptic vesicles, which significantly contribute to dopaminergic neuron degeneration. These results provide in vivo evidence supporting a critical role for dopamine homeostasis in supporting dopaminergic neuron integrity.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Pengxiu
authors.initials: P
authors.lastname: Cao
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Pehek
authors.forename: Alex R
authors.initials: AR
authors.lastname: Moise
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Feng
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000502:physiology; D009410:Nerve Degeneration / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D050493:Vesicular Monoamine Transport Proteins; D051844:alpha-Synuclein; D015102:3,4-Dihydroxyphenylacetic Acid; D049452:Green Fluorescent Proteins; D004298:Dopamine