title: Nigrostriatal dynein changes in A53T alpha-synuclein transgenic mice.
abstract: The accumulation of misfolded a-synuclein is mechanistically linked to neurodegeneration in Parkinson's disease (PD) and other alpha-synucleinopathies. However, how alpha-synuclein causes neurodegeneration is unresolved. Several studies have supported the involvement of dynein, the major motor for retrograde axonal transport in alpha-synuclein-dependent neurodegeneration, especially in the nigrostriatal system. Therefore, we examined the nigrostriatal dyneins in transgenic mice that overexpress human A53T alpha-synuclein and recapitulate key features of a PD-like neuronal synucleinopathy. Age-matched nontransgenic littermates were used as controls. The results demonstrated that the protein level of dynein was decreased in the striatum, whereas it was elevated in the substantia nigra. Double immunostaining results revealed that the reduction in dynein level was associated with aggregation of A53T a-synuclein in the striatum. Furthermore, we performed a quantitative analysis of motor behaviors in A53T alpha-synuclein transgenic mice and controls using a modified open field test. We demonstrated that the protein level of dynein in the striatum was significantly correlated with the motor behaviors. Together, our data indicate that dynein changes in the nigrostriatal system of A53T alpha-synuclein transgenic mice may contribute to their severe movement disorder.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Sun
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen