RRC ID 19172
著者 Hiratsuka T, Matsuzaki S, Miyata S, Kinoshita M, Kakehi K, Nishida S, Katayama T, Tohyama M.
タイトル Yokukansan inhibits neuronal death during ER stress by regulating the unfolded protein response.
ジャーナル PLoS One
Abstract BACKGROUND:Recently, several studies have reported Yokukansan (Tsumura TJ-54), a traditional Japanese medicine, as a potential new drug for the treatment of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress is known to play an important role in the pathogenesis of AD, particularly in neuronal death. Therefore, we examined the effect of Yokukansan on ER stress-induced neurotoxicity and on familial AD-linked presenilin-1 mutation-associated cell death.
METHODS:We employed the WST-1 assay and monitored morphological changes to evaluate cell viability following Yokukansan treatment or treatment with its components. Western blotting and PCR were used to observe the expression levels of GRP78/BiP, caspase-4 and C/EBP homologous protein.
RESULTS:Yokukansan inhibited neuronal death during ER stress, with Cnidii Rhizoma (Senkyu), a component of Yokukansan, being particularly effective. We also showed that Yokukansan and Senkyu affect the unfolded protein response following ER stress and that these drugs inhibit the activation of caspase-4, resulting in the inhibition of ER stress-induced neuronal death. Furthermore, we found that the protective effect of Yokukansan and Senkyu against ER stress could be attributed to the ferulic acid content of these two drugs.
CONCLUSIONS:Our results indicate that Yokukansan, Senkyu and ferulic acid are protective against ER stress-induced neuronal cell death and may provide a possible new treatment for AD.
巻・号 5(10)
ページ e13280
公開日 2010-10-12
DOI 10.1371/journal.pone.0013280
PII e13280
PMID 20967273
PMC PMC2953506
MeSH Animals Apoptosis / drug effects* Cell Line, Tumor Drugs, Chinese Herbal / pharmacology* Endoplasmic Reticulum / metabolism* Endoplasmic Reticulum Chaperone BiP Mice Mutation Neurons / drug effects* Protein Denaturation Signal Transduction
IF 2.74
引用数 24
WOS 分野 NEUROSCIENCES
リソース情報
ヒト・動物細胞 SK-N-SH(RCB0426)