| Title: | Brain p3-Alcβ peptide restores neuronal viability impaired by Alzheimer's amyloid β-peptide |
| Authors: | Hata, Saori Browse this author →KAKEN DB |
| Saito, Haruka Browse this author |
| Kakiuchi, Takeharu Browse this author |
| Fukumoto, Dai Browse this author |
| Yamamoto, Shigeyuki Browse this author |
| Kasuga, Kensaku Browse this author |
| Kimura, Ayano Browse this author |
| Moteki, Koichi Browse this author |
| Abe, Ruriko Browse this author |
| Adachi, Shungo Browse this author |
| Kinoshita, Shoich Browse this author |
| Yoshizawa-Kumagaye, Kumiko Browse this author |
| Nishio, Hideki Browse this author |
| Saito, Takashi Browse this author |
| Saido, Takaomi C. Browse this author |
| Yamamoto, Tohru Browse this author |
| Nishimura, Masaki Browse this author |
| Taru, Hidenori Browse this author →KAKEN DB |
| Sobu, Yuriko Browse this author |
| Ohba, Hiroyuki Browse this author |
| Nishiyama, Shingo Browse this author |
| Harada, Norihiro Browse this author |
| Ikeuchi, Takeshi Browse this author |
| Tsukada, Hideo Browse this author |
| Ouchi, Yasuomi Browse this author |
| Suzuki, Toshiharu Browse this author →KAKEN DB |
| Keywords: | AD therapy |
| alcadein |
| Alzheimer's disease (AD) |
| mitochondria |
| PET imaging |
| Issue Date: | 30-Mar-2023 |
| Publisher: | John Wiley & Sons |
| Journal Title: | EMBO Molecular Medicine |
| Volume: | 15 |
| Issue: | 5 |
| Start Page: | e17052 |
| Publisher DOI: | 10.15252/emmm.202217052 |
| Abstract: | We propose a new therapeutic strategy for Alzheimer's disease (AD). Brain peptide p3-Alc beta 37 is generated from the neuronal protein alcadein beta through cleavage of gamma-secretase, similar to the generation of amyloid beta (A beta) derived from A beta-protein precursor/APP. Neurotoxicity by A beta oligomers (A beta o) is the prime cause prior to the loss of brain function in AD. We found that p3-Alc beta 37 and its shorter peptide p3-Alc beta 9-19 enhanced the mitochondrial activity of neurons and protected neurons against A beta o-induced toxicity. This is due to the suppression of the A beta o-mediated excessive Ca2+ influx into neurons by p3-Alc beta. Successful transfer of p3-Alc beta 9-19 into the brain following peripheral administration improved the mitochondrial viability in the brain of AD mice model, in which the mitochondrial activity is attenuated by increasing the neurotoxic human A beta 42 burden, as revealed through brain PET imaging to monitor mitochondrial function. Because mitochondrial dysfunction is common in the brain of AD patients alongside increased A beta and reduced p3-Alc beta 37 levels, the administration of p3-Alc beta 9-19 may be a promising treatment for restoring, protecting, and promoting brain functions in patients with AD. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/89300 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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