TY - JOUR
T1 - Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology
AU - Ikeda, Masaki
AU - Kawarabayashi, Takeshi
AU - Harigaya, Yasuo
AU - Sasaki, Atsushi
AU - Yamada, Shuichi
AU - Matsubara, Etsuro
AU - Murakami, Tetsuro
AU - Tanaka, Yuya
AU - Kurata, Tomoko
AU - Wuhua, Xu
AU - Ueda, Kenji
AU - Kuribara, Hisashi
AU - Ikarashi, Yasushi
AU - Nakazato, Yoichi
AU - Okamoto, Koichi
AU - Abe, Koji
AU - Shoji, Mikio
N1 - Funding Information:
Grant numbers and sources of supports: Supported by Grant-in-Aid for Grants-in-Aid for Primary Amyloidosis Research Committee (M.S.), from the Ministry of Health, Labor and Welfare of Japan and by Grants-in-Aid for Scientific Research (B) (M.S.: 19390233, K.A.: 18390257), (C) (M.I.: 19590980, T.K.: 19590976, A.S.: 18500276, E.M.: 18590968), from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2009/1/23
Y1 - 2009/1/23
N2 - Missense point mutations, duplication and triplication in the α-synuclein (αSYN) gene have been identified in familial Parkinson's disease (PD). Familial and sporadic PD show common pathological features of αSYN pathologies, e.g., Lewy bodies (LBs) and Lewy neurites (LNs), and a loss of dopaminergic neurons in the substantia nigra that leads to motor disturbances. To elucidate the mechanism of αSYN pathologies, we generated TgαSYN transgenic mice overexpressing human αSYN with double mutations in A30P and A53T. Human αSYN accumulated widely in neurons, processes and aberrant neuronal inclusion bodies. Sarcosyl-insoluble αSYN, as well as phosphorylated, ubiquitinated and nitrated αSYN, was accumulated in the brains. Significantly decreased levels of dopamine (DA) were recognized in the striatum. Motor impairment was revealed in a rotarod test. Thus, TgαSYN is a useful model for analyzing the pathological cascade from aggregated αSYN to motor disturbance, and may be useful for drug trials.
AB - Missense point mutations, duplication and triplication in the α-synuclein (αSYN) gene have been identified in familial Parkinson's disease (PD). Familial and sporadic PD show common pathological features of αSYN pathologies, e.g., Lewy bodies (LBs) and Lewy neurites (LNs), and a loss of dopaminergic neurons in the substantia nigra that leads to motor disturbances. To elucidate the mechanism of αSYN pathologies, we generated TgαSYN transgenic mice overexpressing human αSYN with double mutations in A30P and A53T. Human αSYN accumulated widely in neurons, processes and aberrant neuronal inclusion bodies. Sarcosyl-insoluble αSYN, as well as phosphorylated, ubiquitinated and nitrated αSYN, was accumulated in the brains. Significantly decreased levels of dopamine (DA) were recognized in the striatum. Motor impairment was revealed in a rotarod test. Thus, TgαSYN is a useful model for analyzing the pathological cascade from aggregated αSYN to motor disturbance, and may be useful for drug trials.
KW - Mutation
KW - Neurochemical
KW - Parkinson's disease
KW - Transgenic mouse
KW - α-synuclein
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U2 - 10.1016/j.brainres.2008.10.011
DO - 10.1016/j.brainres.2008.10.011
M3 - Article
C2 - 18992718
AN - SCOPUS:58149468381
SN - 0006-8993
VL - 1250
SP - 232
EP - 241
JO - Molecular Brain Research
JF - Molecular Brain Research
ER -
