title: Cdk5-Dependent Activation of Neuronal Inflammasomes in Parkinson's Disease.
abstract: BACKGROUND
  Inflammasomes, which mediate the activation of caspase-1 and maturation of IL-1β and IL-18, have been unambiguously verified to participate in many diseases, such as lung diseases, infectious diseases and Alzheimer's disease, but the relation between Parkinson's disease and inflammasomes is poorly understood.
  
  
  METHODS
  The expression, maturation, and secretion of inflammasomes in neurons were measured. The activation of inflammasomes in the substantia nigra of the brain was tested in acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and an α-synuclein transgenic mouse model. The levels of IL-1β and IL-18 in cerebrospinal fluid and serum samples of Parkinson's disease (PD) patients and control subjects were measured. The role of cyclin-dependent kinase 5 (Cdk5) in neuronal inflammasome activation was evaluated using the pharmacological Cdk5 inhibitor roscovitine or Cdk5-targeted deletion.
  
  
  RESULTS
  Here, we observed the expression of core molecules of inflammasomes, including NALP3, ASC, caspase-1, and IL-1β, in neuronal cells. The PD inducer rotenone could activate neuronal inflammasomes and promote the maturation and secretion of the cleaved IL-1β and IL-18 in a dose- and time-dependent manner. We also detected the activation of inflammasomes in the substantia nigra of a PD mouse model and in cerebrospinal fluid of PD patients. Furthermore, Cdk5 is required for the activation of inflammasomes, and both inhibition and deletion of Cdk5 could efficiently block inflammasome activation in PD models.
  
  
  CONCLUSIONS
  Together, our results indicated that Cdk5-dependent activation of neuronal inflammasomes was involved in the progression of PD.
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Pei
authors: P
authors: Zhang
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Xiao-Yun
authors: XY
authors: Shao
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Guang-Jian
authors: GJ
authors: Qi
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Qiang
authors: Q
authors: Chen
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Lu-Lu
authors: LL
authors: Bu
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Li-Jun
authors: LJ
authors: Chen
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Jing
authors: J
authors: Shi
authors: Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Jie
authors: J
authors: Ming
authors: Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.|Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei Province, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors: Bo
authors: B
authors: Tian
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse
keywords: Parkinson's disease; cyclin-dependent kinase 5; inflammasome; interleukin 1β