Výsledky vyhledávání - "Hiroki Akashiba"

Discovery of N-ethylpyridine-2-carboxamide derivatives as a novel scaffold for orally active γ-secretase modulators

Autor: Yasuyuki Mitani, Shugo Honda, Shingo Yamasaki, Ryuichi Sekioka, Eriko Honjo, Takayuki Suzuki, Hiroki Akashiba

Publikováno v: Bioorganicmedicinal chemistry. 28(1)

Gamma-secretase modulators (GSMs) are promising disease-modifying drugs for Alzheimer’s disease because they can selectively decrease pathogenic amyloid-β42 (Aβ42) levels. Here we report the discovery of orally active N-ethylpyridine-2-carboxamid

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbacd3edd7ccf6fb78f247a497d7cdc9
https://pubmed.ncbi.nlm.nih.gov/31767402

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Optimization and biological evaluation of imidazopyridine derivatives as a novel scaffold for γ-secretase modulators with oral efficacy against cognitive deficits in Alzheimer’s disease model mice

Autor: Yasuyuki Mitani, Shingo Yamasaki, Junko Yarimizu, Shugo Honda, Ryuichi Sekioka, Hiroki Akashiba

Publikováno v: Bioorganic & Medicinal Chemistry. 28:115455

Gamma-secretase modulators (GSMs) selectively lower amyloid-β42 (Aβ42) and are therefore potential disease-modifying drugs for Alzheimer's disease (AD). Here, we report the discovery of imidazopyridine derivatives as GSMs with oral activity on not

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6cb47e6bba246f5904337a474c7ba8b7
https://doi.org/10.1016/j.bmc.2020.115455

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Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer’s disease

Autor: Kazumi Kimura, Yoshitsugu Shitaka, Shinya Takami, Katsuya Iuchi, Kiyomi Nishimaki, Takashi Yokota, Takuya Kanamaru, Naomi Kamimura, Shigeo Ohta, Ken-ichiro Katsura, Hiroki Akashiba, Masayuki Ueda, Hyunjin Lee

Publikováno v: Brain Research. 1605:49-58

Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer’s disease (AD), stem cell therapy is expected to provide an efficient

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e85fd40761ce273b19e980c6bd0f4398
https://doi.org/10.1016/j.brainres.2015.02.011

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Discovery of novel scaffolds for γ-secretase modulators without an arylimidazole moiety

Autor: Hiroki Akashiba, Ryuichi Sekioka, Eriko Honjo, Shingo Yamasaki, Hideyoshi Fuji, Shugo Honda, Yasuyuki Mitani

Publikováno v: Bioorganicmedicinal chemistry. 26(2)

Gamma-secretase modulators (GSMs) selectively inhibit the production of amyloid-β 42 (Aβ42) and may therefore be useful in the management of Alzheimer’s disease. Most heterocyclic GSMs that are not derived from nonsteroidal anti-inflammatory drug

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::05624c6b8ca3a1d5f8862aaa281ecd03
https://pubmed.ncbi.nlm.nih.gov/29249626

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Pharmacological characterization of the novel γ-secretase modulator AS2715348, a potential therapy for Alzheimer's disease, in rodents and nonhuman primates

Autor: Junko Yarimizu, Yasuyuki Mitani, Yoshitsugu Shitaka, Keni Ni, Mayuko Okabe, Nobuya Matsuoka, Noritoshi Ishikawa, Makoto Asai, Shingo Yamasaki, Hiroshi Uchino, Kyoko Saita, Takashi Nozawa, Hiroki Akashiba

Publikováno v: Neuropharmacology. 79:412-419

γ-Secretase is the enzyme responsible for the intramembranous proteolysis of various substrates, such as amyloid precursor protein (APP) and Notch. Amyloid-β peptide 42 (Aβ42) is produced through the sequential proteolytic cleavage of APP by β- a

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::50d1326744635f86bf4ff6bfa68ae077
https://doi.org/10.1016/j.neuropharm.2013.12.013

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Amelioration of cognitive deficits in plaque-bearing Alzheimer's disease model mice through selective reduction of nascent soluble Aβ42 without affecting other Aβ pools

Autor: Yasuyuki Mitani, Yoshitsugu Shitaka, Nobuya Matsuoka, Junko Yarimizu, Keni Ni, Hiroki Akashiba

Publikováno v: Journal of Neurochemistry. 125:465-472

Given that amyloid-β 42 (Aβ42) is believed to be a culprit in Alzheimer's disease (AD), reducing Aβ42 production should be a potential therapeutic approach. γ-Secretase modulators (GSMs) cause selective reduction of Aβ42 or both reduction of Aβ

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d12a5b1fe356df46ebe12fa41bddfd5
https://doi.org/10.1111/jnc.12125

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Differential Involvement of Cell Cycle Reactivation between Striatal and Cortical Neurons in Cell Death Induced by 3-Nitropropionic Acid

Autor: Hiroki Akashiba, Norio Matsuki, Yuji Ikegaya, Nobuyoshi Nishiyama

Publikováno v: Journal of Biological Chemistry. 283:6594-6606

Recent evidence suggests that unscheduled cell cycle activity leads to neuronal cell death. 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces cell death in both striatum and cerebral cortex. Here we anal

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9288ce5a5d374fc3e5aaab7a4f0481f5
https://doi.org/10.1074/jbc.m707730200

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Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease

Autor: Kazumi Kimura, Yoshitsugu Shitaka, Katsuya Iuchi, Kiyomi Nishimaki, Shinya Takami, Hiroki Akashiba, Shigeo Ohta, Takuya Kanamaru, Naomi Kamimura, Ken-ichiro Katsura, Takashi Yokota

Publikováno v: Neuroscience letters. 587

Oxidative stress is known to play a prominent role in the onset and early stage progression of Alzheimer's disease (AD). For example, protein oxidation and lipid peroxidation levels are increased in patients with mild cognitive impairment. Here, we c

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66a61a2b1896896a10ce30f712f281d9
https://pubmed.ncbi.nlm.nih.gov/25529196

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Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice

Autor: Yasuyuki Mitani, Yoshitsugu Shitaka, Hiroshi Uchino, Keni Ni, Junko Yarimizu, Kyoko Saita, Hiroki Akashiba, Nobuya Matsuoka

Publikováno v: The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(6)

γ-Secretase inhibitors (GSIs) reduce amyloid-β (Aβ) peptides but inevitably increase the β-C-terminal fragment (β-CTF) of amyloid precursor protein (APP), potentially having undesirable effects on synapses. In contrast, γ-secretase modulators (

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f4862f6ba722365ffd10b683e6b180a2
https://pubmed.ncbi.nlm.nih.gov/22323718

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Ablation of p27 enhance kainate-induced seizure and hippocampal degeneration

Autor: Keiko Nakayama, Norio Matsuki, Chihiro Ueyama, Keiichi I. Nakayama, Hiroki Akashiba, Nobuyoshi Nishiyama

Publikováno v: Neuroreport. 18(17)

p27 is a cyclin-dependent kinase inhibitor which arrests cell cycle at G 1 -S phase. Using RNA interference method, we previously showed that reduction of endogenous p27 expression induces cell death through cell cycle progression in cultured cortica

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f08b2f1c81921d650ce19715c7b7764
https://pubmed.ncbi.nlm.nih.gov/18090311

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