Pharmacological properties of a novel and potent γ-secretase modulator as a therapeutic option for the treatment of Alzheimer’s disease
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- 作者：Koji Murakamia ; Tomomichi Watanabea ; Tatsuki Koikea ; Makoto Kamataa ; Tomoko Igarib ; Shinichi Kondoa ; shinichi.kondou@takeda.com" class="auth_mail" title="E-mail the corresponding author
- 关键词：Aβ ; Amyloid-β ; AD ; Alzheimer&rsquo ; s disease ; APP ; Amyloid precursor protein ; β-CTF ; β-C-terminal fragment ; BACE ; β-site APP-cleaving enzyme ; CSF ; Cerebrospinal fluid ; ELISA ; Enzyme-linked immunosorbent assay ; FBS ; Fetal bovine serum ; GSI ; γ-secretase inhibitor ; GSM ; γ-secretase modulator ; LC/MS/MS ; Liquid chromatography-tandem mass spectrometry ; N2a-APPsw ; Neuro-2a mouse neuroblastoma cells stably expressing human Swedish mutant APP ; NFT ; Neurofibrillary tangle ; NORT ; Novel object recognition t
- 刊名：Brain Research
- 出版年：2016
- 出版时间：15 February 2016
- 年：2016
- 卷：1633
- 期：Complete
- 页码：73-86
- 全文大小：1142 K
文摘
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Compound-1 modulated γ-secretase activity and significantly reduced Aβ40 and Aβ42.
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Compound-1 inhibited Aβ deposition.
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Compound-1 ameliorated cognitive impairments in a mouse model of AD.
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The efficacy of compound-1 was maintained even after drug withdrawal.
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Compound-1 showed no adverse effect evoked by GSI and Notch-sparing GSIs.