論文

査読有り 国際誌
2019年1月

Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging.

Molecular neurobiology
  • Yukiko Miyazaki
  • ,
  • Takeshi Ishikawa
  • ,
  • Yuji O Kamatari
  • ,
  • Takehiro Nakagaki
  • ,
  • Hanae Takatsuki
  • ,
  • Daisuke Ishibashi
  • ,
  • Kazuo Kuwata
  • ,
  • Noriyuki Nishida
  • ,
  • Ryuichiro Atarashi

56
1
開始ページ
367
終了ページ
377
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s12035-018-1088-7

Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein (PrPSc) in the central nervous system. Although several small compounds that bind to normal PrP (PrPC) have been shown to inhibit structural conversion of the protein, an effective therapy for human prion disease remains to be established. In this study, we screened 1200 existing drugs approved by the US Food and Drug Administration (FDA) for anti-prion activity using surface plasmon resonance imaging (SPRi). Of these drugs, 31 showed strong binding activity to recombinant human PrP, and three of these reduced the accumulation of PrPSc in prion-infected cells. One of the active compounds, alprenolol hydrochloride, which is used clinically as a β-adrenergic blocker for hypertension, also reduced the accumulation of PrPSc in the brains of prion-infected mice at the middle stage of the disease when the drug was administered orally with their daily water from the day after infection. Docking simulation analysis suggested that alprenolol hydrochloride fitted into the hotspot within mouse PrPC, which is known as the most fragile structure within the protein. These findings provide evidence that SPRi is useful in identifying effective drug candidates for neurodegenerative diseases caused by abnormal protein aggregation, such as prion diseases.

リンク情報
DOI
https://doi.org/10.1007/s12035-018-1088-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29704200
ID情報
  • DOI : 10.1007/s12035-018-1088-7
  • ISSN : 0893-7648
  • PubMed ID : 29704200

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