JP2021138656A - 神経突起伸長促進剤、神経細胞の樹状突起発現促進剤、及び神経栄養因子様作用物質 - Google Patents
神経突起伸長促進剤、神経細胞の樹状突起発現促進剤、及び神経栄養因子様作用物質 Download PDFInfo
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Abstract
Description
・環状ペプチド誘導体:特許文献3(WO2016/047638)の実施例に記載の方法により得られた上記式(2)で表される化合物のジエチルアミン塩。
・NGF(nerve growth factor):シグマ アルドリッチ ジャパンより入手
・VGF(VGF nerve growth factor inducible:栄養因子の1つ、NGFより誘導される):PHENIX PHARMACEUTICALS, INC.より入手
基本プロトコール(Culturing hippocampal neurons(Stefanie et al.))を改変して行った。
NPM:MEM supplemented with glucose(0.6% (wt/vol) and containing 10%(vol/vol)horse serum)。MEM with Earle’s saltsand L-glutamine (Invitrogen 11095-080), D-Glucose (Sigma G8769), Horse serum(KOJ 12180110)
CMF−HBSS:Calcium-,magnesium-,and bicarbonate-free Hank’sbalanced salt solution (BSS) with 10 mM HEPES, pH 7.3。10XHank’s BSS (Invitrogen 14185-052), 1M HEPES buffer, pH 7.3, (Invitrogen15630-080)
上記のようにしてマウス胎児の海馬より初代培養法を用いて海馬ニューロンを播種し3時間後、かかる培養直後の海馬ニューロン(未発達状態)に環状ペプチド誘導体をNB培地に溶解したものを添加し、3日間培養した。培養後に写真撮影を行い、海馬ニューロンに対する影響を評価した。
(1)実施例1(環状ペプチド誘導体の神経細胞に及ぼす影響)
環状ペプチド誘導体の濃度と神経細胞における樹状突起(このタイプの神経細胞をデンドライトと呼ぶ)の長さの関連を評価した。図1に示したように、環状ペプチド誘導体濃度が0.03μMから0.3μMまで濃度依存的に1個の神経細胞における樹状突起の長さは増加した。また、図2にみられるように、樹状突起数もまた0.03μMから1.0μMまで濃度依存的に増加した。さらに、図3に示したように、デンドロライトにおける軸索長についても評価したところ、0.03μMから0.1μMと環状ペプチド誘導体を添加したところ、軸索長は有意(P < 0.01、 P < 0.001、 P < 0.0001)に増加した。
従来の神経栄養因子剤として知られているNGF(Nerve growth factor)、および抗うつ剤として期待されている神経栄養因子のVGF(Non-acronymic neuropeptide factor)と比較評価した。
Claims (6)
- 前記一般式(1)において、R1、R2、R3およびR4はそれぞれ独立にアルキル基であり、n=2〜4であり、R5およびR6はそれぞれ水素原子であり、R7およびR8はそれぞれ独立にカルボキシ基またはその塩である、請求項1に記載の神経突起伸長促進剤。
- 前記一般式(1)において、R1、R2、R3およびR4はそれぞれ独立にアルキル基であり、n=2〜4であり、R5およびR6はそれぞれ水素原子であり、R7およびR8はそれぞれ独立にカルボキシ基またはその塩である、請求項3に記載の樹状突起発現促進剤。
- 前記一般式(1)において、R1、R2、R3およびR4はそれぞれ独立にアルキル基であり、n=2〜4であり、R5およびR6はそれぞれ水素原子であり、R7およびR8はそれぞれ独立にカルボキシ基またはその塩である、請求項5に記載の神経栄養因子様作用物質。
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Cited By (5)
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WO2022231002A1 (ja) | 2021-04-28 | 2022-11-03 | 東レ株式会社 | 中空糸膜およびその製造方法 |
WO2024029630A1 (ja) * | 2022-08-04 | 2024-02-08 | 第一工業製薬株式会社 | 環状ペプチド誘導体とその製造方法および組成物 |
WO2024071370A1 (ja) * | 2022-09-30 | 2024-04-04 | 第一工業製薬株式会社 | 眼科疾患を処置または予防するための環状ペプチド誘導体組成物 |
WO2024096066A1 (ja) * | 2022-11-04 | 2024-05-10 | 第一工業製薬株式会社 | 中枢神経系損傷疾患を処置または予防するための環状ペプチド誘導体組成物 |
WO2024096067A1 (ja) * | 2022-11-04 | 2024-05-10 | 第一工業製薬株式会社 | 神経障害性疼痛および/または炎症性疼痛を処置または予防するための環状ペプチド誘導体組成物 |
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WO2022231002A1 (ja) | 2021-04-28 | 2022-11-03 | 東レ株式会社 | 中空糸膜およびその製造方法 |
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WO2024096066A1 (ja) * | 2022-11-04 | 2024-05-10 | 第一工業製薬株式会社 | 中枢神経系損傷疾患を処置または予防するための環状ペプチド誘導体組成物 |
WO2024096067A1 (ja) * | 2022-11-04 | 2024-05-10 | 第一工業製薬株式会社 | 神経障害性疼痛および/または炎症性疼痛を処置または予防するための環状ペプチド誘導体組成物 |
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