Brain p3-Alcβ peptide restores neuronal viability impaired by Alzheimer's amyloid β-peptide

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 activi

SUBMITTER: Dr. Saori Hata 

PROVIDER: S-SCDT-10_15252-EMMM_202217052 | biostudies-other |

REPOSITORIES: biostudies-other