Accumulation of beta- and gamma-synucleins in the ubiquitin carboxyl-terminal hydrolase L1-deficient gad mouse.
The synuclein family includes three isoforms, termed alpha, beta and gamma. alpha-Synuclein accumulates in various pathological lesions resulting from neurodegenerative disorders including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. However, neither beta- nor gamma-synuclein has been detected in Lewy bodies, and thus it is unclear whether these isoforms contribute to neurological pathology. In the present study, we used immunohistochemistry to demonstrate accelerated accumulation of beta- and gamma-synucleins in axonal spheroids in gracile axonal dystrophy (gad) mice, which do not express ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1). gamma-Synuclein immunoreactivity in the spheroids appeared in the gracile nucleus at 3 weeks of age and was maintained until 32 weeks. beta-Synuclein immunoreactivity appeared in spheroids around 12 weeks of age. In contrast, alpha-synuclein immunoreactivity was barely detectable in spheroids. Immunoreactivity for synaptophysin and ubiquitin were either faint or undetectable in spheroids. Given that UCH-L1 deficiency results in axonal degeneration and spheroid formation, our findings suggest that beta- and gamma-synuclein participate in the pathogenesis of axonal swelling in gad mice.
Wang
Yu-Lai
YL
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
Takeda
Ayako
A
Osaka
Hitoshi
H
Hara
Yoko
Y
Furuta
Akiko
A
Setsuie
Rieko
R
Sun
Ying-Jie
YJ
Kwon
Jungkee
J
Sato
Yae
Y
Sakurai
Mikako
M
Noda
Mami
M
Yoshikawa
Yasuhiro
Y
Wada
Keiji
K
D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D008526:Medulla Oblongata / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051843:Synucleins; D043222:Ubiquitin Thiolesterase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D051844:alpha-Synuclein; D051846:beta-Synuclein; D051845:gamma-Synuclein
D009419:Nerve Tissue Proteins; C497605:Snca protein, mouse; C497608:Sncb protein, mouse; D051843:Synucleins; C482860:UCHL1 protein, human; D051844:alpha-Synuclein; D051846:beta-Synuclein; D051845:gamma-Synuclein; D043222:Ubiquitin Thiolesterase