title: A Novel Immunosuppressor, (5R)-5-Hydroxytriptolide, Alleviates Movement Disorder and Neuroinflammation in a 6-OHDA Hemiparkinsonian Rat Model.
abstract: Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. Promising therapies for PD still need to be explored. Immune dysfunction has been found to be involved in PD pathogenesis. Here, a novel immunosuppressor, (5R)-5-hydroxytriptolide (LLDT8), was used to treat 6-hydroxydopamine (6-OHDA)-induced hemiparkinson rats. We found that oral administration of LLDT8 significantly alleviated apomorphine-induced rotations at a dose of 125 µg/kg, and improved performance in cylinder and rotarod tests at a lower dose of 31.25 µg/kg, in 6-OHDA hemiparkinsonian rats. Moreover, loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the 6-OHDA rat was attenuated in response to LLDT8 treatment in a dose-dependent manner. In addition, inflammatory factors IL-1β, IL-6 and TNF-α, were significantly inhibited in LLDT8-treated hemiparkisonian rats, compared with vehicle. Notably, the level of dopamine (DA) in the striatum of PD rats was restored by LLDT8 treatment. Furthermore, we also detected that the disequilibrium of peripheral lymphocytes was reversed by LLDT8 administration. Taken together, the results imply that the immunosuppressor, LLDT8, can rescue dopaminergic neurodegeneration in 6-OHDA hemiparkinsonian rats, thus providing a potential therapeutic strategy for PD.
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Su
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Zhen
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Qian
authors.affiliation: 1Department of Physiology,; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: 2Department of Neurobiology, and; 3Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.; 4Beijing Institute for Brain Disorders, Beijing100069, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
keywords: (5R)-5-hydroxytriptolide; Parkinson’s disease; immunosuppressor; neuroinflammation