Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is recapitulated in alpha-synuclein transgenic Drosophila.
alpha-Synuclein is a major component of Lewy bodies in the brains of patients with Parkinson's disease (PD) as well as of neuronal/glial inclusions in a subset of neurodegenerative disorders collectively termed synucleinopathies. Here we studied by immunohistochemistry the accumulation of alpha-synuclein in transgenic (TG) Drosophila overexpressing wild-type (WT) or familial PD-linked mutant (i.e. A30P and A53T) alpha-synuclein in neurons, with special reference to the phosphorylation at Ser129, that is characteristic of human synucleinopathy lesions. Progressive accumulation of human alpha-synuclein was widely observed in the cell bodies and neurites of major neuronal nuclei in TG Drosophila brains, and phosphorylation of alpha-synuclein at Ser129 was detected in a limited subset of neurons approximately 1 week after alpha-synuclein immunoreactivity was first detected. Phosphorylated alpha-synuclein was most abundant in A53T mutant, followed by A30P and WT Drosophila. These results suggest that accumulation and phosphorylation of alpha-synuclein is recapitulated in neurons of alpha-synuclein transgenic Drosophila, that underscores the relevance of this model to human synucleinopatheis.
Takahashi
Makio
M
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kanuka
Hirotaka
H
Fujiwara
Hideo
H
Koyama
Akihiko
A
Hasegawa
Masato
M
Miura
Masayuki
M
Iwatsubo
Takeshi
T
D000818:Animals; D004330:Drosophila; D007150:Immunohistochemistry; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D051843:Synucleins; D013997:Time Factors; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein; D012694:Serine