Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A₂A receptor and ubiquitin proteasome system.

Abstract:

ETHNOPHARMACOLOGICAL RELEVANCE: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. AIM OF THE STUDY:To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). MATERIALS AND 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. CONCLUSION:Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A(2A)-R through PKA-dependent pathway.

journal_name

J Ethnopharmacol

authors

Huang CL,Yang JM,Wang KC,Lee YC,Lin YL,Yang YC,Huang NK

doi

10.1016/j.jep.2011.08.075

subject

Has Abstract

pub_date

2011-10-31 00:00:00

pages

162-8

issue

1

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(11)00648-9

journal_volume

138

pub_type

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