Reference - Detail
| RRC ID | 87294 |
|---|---|
| Author | Hata S, Saito H, Kakiuchi T, Fukumoto D, Yamamoto S, Kasuga K, Kimura A, Moteki K, Abe R, Adachi S, Kinoshita S, Yoshizawa-Kumagaye K, Nishio H, Saito T, Saido TC, Yamamoto T, Nishimura M, Taru H, Sobu Y, Ohba H, Nishiyama S, Harada N, Ikeuchi T, Tsukada H, Ouchi Y, Suzuki T. |
| Title | Brain p3-Alcβ peptide restores neuronal viability impaired by Alzheimer's amyloid β-peptide. |
| Journal | EMBO Mol Med |
| Abstract |
We propose a new therapeutic strategy for Alzheimer's disease (AD). Brain peptide p3-Alcβ37 is generated from the neuronal protein alcadein β through cleavage of γ-secretase, similar to the generation of amyloid β (Aβ) derived from Aβ-protein precursor/APP. Neurotoxicity by Aβ oligomers (Aβo) is the prime cause prior to the loss of brain function in AD. We found that p3-Alcβ37 and its shorter peptide p3-Alcβ9-19 enhanced the mitochondrial activity of neurons and protected neurons against Aβo-induced toxicity. This is due to the suppression of the Aβo-mediated excessive Ca2+ influx into neurons by p3-Alcβ. Successful transfer of p3-Alcβ9-19 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 Aβ42 burden, as revealed through brain PET imaging to monitor mitochondrial function. Because mitochondrial dysfunction is common in the brain of AD patients alongside increased Aβ and reduced p3-Alcβ37 levels, the administration of p3-Alcβ9-19 may be a promising treatment for restoring, protecting, and promoting brain functions in patients with AD. |
| Volume | 15(5) |
| Pages | e17052 |
| Published | 2023-5-8 |
| DOI | 10.15252/emmm.202217052 |
| PMID | 36994913 |
| PMC | PMC10165357 |
| MeSH | Alzheimer Disease* / drug therapy Alzheimer Disease* / metabolism Amyloid Precursor Protein Secretases / metabolism Amyloid beta-Peptides* / metabolism Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism Animals Brain / metabolism Humans Intercellular Signaling Peptides and Proteins Mice Neurons / metabolism |
| IF | 8.821 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC06343 RBRC06344 |