Alpha-synuclein induces apoptosis by altered expression in human peripheral lymphocyte in Parkinson's disease.
Though the etiology of Parkinson's disease (PD) remains unclear, alpha-synuclein (alpha-SN) is regarded as a major causative agent of PD. Several lines of evidence indicate that immunological abnormalities are associated with PD for unknown reasons. The present study was performed to assess whether peripheral blood mononuclear cells (PBMCs) show altered alpha-SN expression in PD patients and to identify its functions, which may be related to peripheral immune abnormalities in PD. alpha-SN was found to be expressed more in 151 idiopathic PD (IPD) patients than in 101 healthy controls, who nevertheless showed as age-dependent increases. By in vitro transfection, alpha-SN expression was shown to be correlated with glucocorticoid sensitive apoptosis, possibly caused by the enhanced expression of glucocorticoid receptor (GR), caspase activations (caspase-8, caspase-9), CD95 up-regulation, and reactive oxygen species (ROS) production. An understanding of the correlation between alpha-SN levels and apoptosis in the presence of the coordinated involvement of multiple processes would provide an insight into the molecular basis of the disease. The present study provides a clue that the alpha-SN may be one of the primary causes of the immune abnormalities observed in PD and offers new targets for pharmacotherapeutic intervention.
Kim
Seonghan
S
Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Republic of Korea.
Jeon
Beom S
BS
Heo
Chaejeong
C
Im
Pil Seon
PS
Ahn
Tae-Beom
TB
Seo
Ji-Heui
JH
Kim
Hye-Sun
HS
Park
Cheol Hyoung
CH
Choi
Se Hoon
SH
Cho
Seo-Hyun
SH
Lee
Wang Jae
WJ
Suh
Yoo-Hun
YH
D017209:Apoptosis; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D011965:Receptors, Glucocorticoid; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D019014:fas Receptor; D020169:Caspases