| First Author | Hata S | Year | 2023 |
| Journal | EMBO Mol Med | Volume | 15 |
| Issue | 5 | Pages | e17052 |
| PubMed ID | 36994913 | Mgi Jnum | J:339205 |
| Mgi Id | MGI:7481404 | Doi | 10.15252/emmm.202217052 |
| Citation | Hata S, et al. (2023) Brain p3-Alcbeta peptide restores neuronal viability impaired by Alzheimer's amyloid beta-peptide. EMBO Mol Med 15(5):e17052 |
| abstractText | We propose a new therapeutic strategy for Alzheimer's disease (AD). Brain peptide p3-Alcbeta37 is generated from the neuronal protein alcadein beta through cleavage of gamma-secretase, similar to the generation of amyloid beta (Abeta) derived from Abeta-protein precursor/APP. Neurotoxicity by Abeta oligomers (Abetao) is the prime cause prior to the loss of brain function in AD. We found that p3-Alcbeta37 and its shorter peptide p3-Alcbeta9-19 enhanced the mitochondrial activity of neurons and protected neurons against Abetao-induced toxicity. This is due to the suppression of the Abetao-mediated excessive Ca(2+) influx into neurons by p3-Alcbeta. Successful transfer of p3-Alcbeta9-19 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 Abeta42 burden, as revealed through brain PET imaging to monitor mitochondrial function. Because mitochondrial dysfunction is common in the brain of AD patients alongside increased Abeta and reduced p3-Alcbeta37 levels, the administration of p3-Alcbeta9-19 may be a promising treatment for restoring, protecting, and promoting brain functions in patients with AD. |
