Proteomics of Caenorhabditis elegans over-expressing human alpha-synuclein analyzed by fluorogenic derivatization-liquid chromatography/tandem mass spectrometry: identification of actin and several ribosomal proteins as negative markers at early Parkinson's disease stages.
It has been known that the over-expression of alpha-synuclein, the main protein of Lewy bodies in Parkinson's disease (PD), leads to neurodegeneration in PD models. In this study, the changes in protein expression between the transgenic over-expressing human alpha-synuclein wild type (alpha-synWT) and the control Caenorhabditis elegans were elucidated by fluorogenic derivatization-liquid chromatography/tandem mass spectrometry (FD-LC-MS/MS) proteome analysis, which is a highly selective, sensitive, repeatable and quantitative method for protein identification. Because the alpha-synuclein wild-type worms showed moderate levels of dopamine loss without overt behavioral abnormalities, it was suggested that the changes in proteins in the alpha-synWT are related in the sequence of the formation of Lewy bodies. Among more than 400 protein peaks detected, actin and several ribosomal proteins were identified for the first time as negative markers at early PD stages. Actin was suggested to be one of the important targets in the elucidation of the etiology of neuronal diseases such as PD or other synucleinopathies.
Ichibangase
Tomoko
T
Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Saimaru
Hiroshi
H
Takamura
Norio
N
Kuwahara
Tomoki
T
Koyama
Akihiko
A
Iwatsubo
Takeshi
T
Imai
Kazuhiro
K
D000199:Actins / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism*; D040901:Proteomics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D015415:Biomarkers; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D051844:alpha-Synuclein