title: Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A₂A receptor and ubiquitin proteasome system.
abstract: BACKGROUND
  Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect.
  
  
  OBJECTIVE
  To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD).
  
  
  METHODS
  MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope.
  
  
  RESULTS
  This protection of Gastrodia elata could be blocked by an A(2A)-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A(2A)-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A(2A)-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations.
  
  
  CONCLUSIONS
  Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A(2A)-R through PKA-dependent pathway.
authors.affiliation: Medical Research Center, Cardinal Tien Hospital, Hsintien, New Taipei County, Taiwan, ROC.
authors.forename: Chuen-Lin
authors.initials: CL
authors.lastname: Huang
authors.forename: Jung-Mou
authors.initials: JM
authors.lastname: Yang
authors.forename: Kaw-Chen
authors.initials: KC
authors.lastname: Wang
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Lee
authors.forename: Yun-Lian
authors.initials: YL
authors.lastname: Lin
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Yang
authors.forename: Nai-Kuei
authors.initials: NK
authors.lastname: Huang
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology; D031668:Gastrodia; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy; D007976:Leupeptins / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D008517:Phytotherapy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D015853:Cysteine Proteinase Inhibitors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D007976:Leupeptins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D043705:Receptor, Adenosine A2A; D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde