Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging
Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) have been shown to in...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Miyazaki, Yukiko [verfasserIn] Ishikawa, Takeshi [verfasserIn] Kamatari, Yuji O. [verfasserIn] Nakagaki, Takehiro [verfasserIn] Takatsuki, Hanae [verfasserIn] Ishibashi, Daisuke [verfasserIn] Kuwata, Kazuo [verfasserIn] Nishida, Noriyuki [verfasserIn] Atarashi, Ryuichiro [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Molecular neurobiology - Totowa, NJ : Humana Press, 1987, 56(2018), 1 vom: 27. Apr., Seite 367-377 |
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| Übergeordnetes Werk: |
volume:56 ; year:2018 ; number:1 ; day:27 ; month:04 ; pages:367-377 |
| Links: |
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| DOI / URN: |
10.1007/s12035-018-1088-7 |
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| Katalog-ID: |
SPR023982446 |
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| 520 | |a Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, which is known as the most fragile structure within the protein. These findings provide evidence that SPRi is useful in identifying effective drug candidates for neurodegenerative diseases caused by abnormal protein aggregation, such as prion diseases. | ||
| 650 | 4 | |a Prion diseases |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Surface plasmon resonance imaging |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Alprenolol hydrochloride |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Docking simulation |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Ishikawa, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a Kamatari, Yuji O. |e verfasserin |4 aut | |
| 700 | 1 | |a Nakagaki, Takehiro |e verfasserin |4 aut | |
| 700 | 1 | |a Takatsuki, Hanae |e verfasserin |4 aut | |
| 700 | 1 | |a Ishibashi, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Kuwata, Kazuo |e verfasserin |4 aut | |
| 700 | 1 | |a Nishida, Noriyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Atarashi, Ryuichiro |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:56 |g year:2018 |g number:1 |g day:27 |g month:04 |g pages:367-377 |
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10.1007/s12035-018-1088-7 doi (DE-627)SPR023982446 (SPR)s12035-018-1088-7-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Miyazaki, Yukiko verfasserin aut Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, 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. Prion diseases (dpeaa)DE-He213 Surface plasmon resonance imaging (dpeaa)DE-He213 Alprenolol hydrochloride (dpeaa)DE-He213 Docking simulation (dpeaa)DE-He213 Ishikawa, Takeshi verfasserin aut Kamatari, Yuji O. verfasserin aut Nakagaki, Takehiro verfasserin aut Takatsuki, Hanae verfasserin aut Ishibashi, Daisuke verfasserin aut Kuwata, Kazuo verfasserin aut Nishida, Noriyuki verfasserin aut Atarashi, Ryuichiro verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2018), 1 vom: 27. Apr., Seite 367-377 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2018 number:1 day:27 month:04 pages:367-377 https://dx.doi.org/10.1007/s12035-018-1088-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2018 1 27 04 367-377 |
| spelling |
10.1007/s12035-018-1088-7 doi (DE-627)SPR023982446 (SPR)s12035-018-1088-7-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Miyazaki, Yukiko verfasserin aut Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, 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. Prion diseases (dpeaa)DE-He213 Surface plasmon resonance imaging (dpeaa)DE-He213 Alprenolol hydrochloride (dpeaa)DE-He213 Docking simulation (dpeaa)DE-He213 Ishikawa, Takeshi verfasserin aut Kamatari, Yuji O. verfasserin aut Nakagaki, Takehiro verfasserin aut Takatsuki, Hanae verfasserin aut Ishibashi, Daisuke verfasserin aut Kuwata, Kazuo verfasserin aut Nishida, Noriyuki verfasserin aut Atarashi, Ryuichiro verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2018), 1 vom: 27. Apr., Seite 367-377 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2018 number:1 day:27 month:04 pages:367-377 https://dx.doi.org/10.1007/s12035-018-1088-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2018 1 27 04 367-377 |
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10.1007/s12035-018-1088-7 doi (DE-627)SPR023982446 (SPR)s12035-018-1088-7-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Miyazaki, Yukiko verfasserin aut Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, 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. Prion diseases (dpeaa)DE-He213 Surface plasmon resonance imaging (dpeaa)DE-He213 Alprenolol hydrochloride (dpeaa)DE-He213 Docking simulation (dpeaa)DE-He213 Ishikawa, Takeshi verfasserin aut Kamatari, Yuji O. verfasserin aut Nakagaki, Takehiro verfasserin aut Takatsuki, Hanae verfasserin aut Ishibashi, Daisuke verfasserin aut Kuwata, Kazuo verfasserin aut Nishida, Noriyuki verfasserin aut Atarashi, Ryuichiro verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2018), 1 vom: 27. Apr., Seite 367-377 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2018 number:1 day:27 month:04 pages:367-377 https://dx.doi.org/10.1007/s12035-018-1088-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2018 1 27 04 367-377 |
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10.1007/s12035-018-1088-7 doi (DE-627)SPR023982446 (SPR)s12035-018-1088-7-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Miyazaki, Yukiko verfasserin aut Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, 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. Prion diseases (dpeaa)DE-He213 Surface plasmon resonance imaging (dpeaa)DE-He213 Alprenolol hydrochloride (dpeaa)DE-He213 Docking simulation (dpeaa)DE-He213 Ishikawa, Takeshi verfasserin aut Kamatari, Yuji O. verfasserin aut Nakagaki, Takehiro verfasserin aut Takatsuki, Hanae verfasserin aut Ishibashi, Daisuke verfasserin aut Kuwata, Kazuo verfasserin aut Nishida, Noriyuki verfasserin aut Atarashi, Ryuichiro verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2018), 1 vom: 27. Apr., Seite 367-377 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2018 number:1 day:27 month:04 pages:367-377 https://dx.doi.org/10.1007/s12035-018-1088-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2018 1 27 04 367-377 |
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10.1007/s12035-018-1088-7 doi (DE-627)SPR023982446 (SPR)s12035-018-1088-7-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Miyazaki, Yukiko verfasserin aut Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, 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. Prion diseases (dpeaa)DE-He213 Surface plasmon resonance imaging (dpeaa)DE-He213 Alprenolol hydrochloride (dpeaa)DE-He213 Docking simulation (dpeaa)DE-He213 Ishikawa, Takeshi verfasserin aut Kamatari, Yuji O. verfasserin aut Nakagaki, Takehiro verfasserin aut Takatsuki, Hanae verfasserin aut Ishibashi, Daisuke verfasserin aut Kuwata, Kazuo verfasserin aut Nishida, Noriyuki verfasserin aut Atarashi, Ryuichiro verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2018), 1 vom: 27. Apr., Seite 367-377 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2018 number:1 day:27 month:04 pages:367-377 https://dx.doi.org/10.1007/s12035-018-1088-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2018 1 27 04 367-377 |
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Enthalten in Molecular neurobiology 56(2018), 1 vom: 27. Apr., Seite 367-377 volume:56 year:2018 number:1 day:27 month:04 pages:367-377 |
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Enthalten in Molecular neurobiology 56(2018), 1 vom: 27. Apr., Seite 367-377 volume:56 year:2018 number:1 day:27 month:04 pages:367-377 |
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Prion diseases Surface plasmon resonance imaging Alprenolol hydrochloride Docking simulation |
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Molecular neurobiology |
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Miyazaki, Yukiko @@aut@@ Ishikawa, Takeshi @@aut@@ Kamatari, Yuji O. @@aut@@ Nakagaki, Takehiro @@aut@@ Takatsuki, Hanae @@aut@@ Ishibashi, Daisuke @@aut@@ Kuwata, Kazuo @@aut@@ Nishida, Noriyuki @@aut@@ Atarashi, Ryuichiro @@aut@@ |
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2018-04-27T00:00:00Z |
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Docking simulation analysis suggested that alprenolol hydrochloride fitted into the hotspot within mouse $ PrP^{C} $, which is known as the most fragile structure within the protein. 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Miyazaki, Yukiko |
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Miyazaki, Yukiko ddc 610 bkl 44.90 misc Prion diseases misc Surface plasmon resonance imaging misc Alprenolol hydrochloride misc Docking simulation Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging |
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610 570 ASE 44.90 bkl Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging Prion diseases (dpeaa)DE-He213 Surface plasmon resonance imaging (dpeaa)DE-He213 Alprenolol hydrochloride (dpeaa)DE-He213 Docking simulation (dpeaa)DE-He213 |
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ddc 610 bkl 44.90 misc Prion diseases misc Surface plasmon resonance imaging misc Alprenolol hydrochloride misc Docking simulation |
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Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging |
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Miyazaki, Yukiko Ishikawa, Takeshi Kamatari, Yuji O. Nakagaki, Takehiro Takatsuki, Hanae Ishibashi, Daisuke Kuwata, Kazuo Nishida, Noriyuki Atarashi, Ryuichiro |
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Miyazaki, Yukiko |
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identification of alprenolol hydrochloride as an anti-prion compound using surface plasmon resonance imaging |
| title_auth |
Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging |
| abstract |
Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, which is known as the most fragile structure within the protein. These findings provide evidence that SPRi is useful in identifying effective drug candidates for neurodegenerative diseases caused by abnormal protein aggregation, such as prion diseases. |
| abstractGer |
Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, which is known as the most fragile structure within the protein. These findings provide evidence that SPRi is useful in identifying effective drug candidates for neurodegenerative diseases caused by abnormal protein aggregation, such as prion diseases. |
| abstract_unstemmed |
Abstract Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein ($ PrP^{Sc} $) in the central nervous system. Although several small compounds that bind to normal PrP ($ PrP^{C} $) 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 $ PrP^{Sc} $ 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 $ PrP^{Sc} $ 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 $ PrP^{C} $, 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. |
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Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging |
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Ishikawa, Takeshi Kamatari, Yuji O. Nakagaki, Takehiro Takatsuki, Hanae Ishibashi, Daisuke Kuwata, Kazuo Nishida, Noriyuki Atarashi, Ryuichiro |
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| score |
7.4013777 |