RRC ID 12309
著者 Matsui H, Ito H, Taniguchi Y, Takeda S, Takahashi R.
タイトル Ammonium chloride and tunicamycin are novel toxins for dopaminergic neurons and induce Parkinson's disease-like phenotypes in medaka fish.
ジャーナル J Neurochem
Abstract Perturbations in protein folding and degradation are key pathological mechanisms in neurodegenerative diseases, including Parkinson's disease (PD). Recent evidence suggests that mishandling of proteins may play an important role in the pathogenesis of PD. We have utilized medaka fish to monitor the effects of injecting neurotoxins into the CSF space. In this study, ammonium chloride, tunicamycin, and lactacystin were tested for their ability to disturb lysosomal proteolysis, N-glycosylation in the endoplasmic reticulum, and proteasomal degradation, respectively. All of the substances tested induced selective loss of dopaminergic neurons, movement disorders and inclusion bodies. Among them, the features of the inclusion bodies that developed after ammonium chloride injection mimicked those of PD: co-localization of ubiquitin and phosphorylated α-synuclein, as well as the presence of LC3 protein in the inclusion bodies. Our study demonstrated that medaka fish are useful for examining the effects of environmental toxins and lysosome inhibition, and lysosome inhibitors may be factors in the development of PD.
巻・号 115(5)
ページ 1150-60
公開日 2010-12-1
DOI 10.1111/j.1471-4159.2010.07012.x
PMID 21219329
MeSH Acetylcysteine / analogs & derivatives Acetylcysteine / toxicity Ammonium Chloride / toxicity Animals Disease Models, Animal Dopamine / physiology* Nerve Tissue Proteins / metabolism Neurons / drug effects* Neurons / pathology Neurotoxins / toxicity* Oryzias / anatomy & histology Oryzias / physiology* Parkinsonian Disorders / chemically induced* Parkinsonian Disorders / pathology Parkinsonian Disorders / physiopathology Phenotype* Substantia Nigra / drug effects* Substantia Nigra / pathology Substantia Nigra / physiopathology Tunicamycin / toxicity
IF 4.066
引用数 13
WOS 分野 NEUROSCIENCES BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
メダカ Kyoto-cab (OK-Cab (MT830))