Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease

Khavinson V, Ilina A, Kraskovskaya N, Linkova N, Kolchina N, Mironova E, Erofeev A, Petukhov M. Pharmaceuticals (Basel). 2021.

Organ: brain-cognition · Type: in-vivo · Peptides: EDR, KED

PMID: 34071923

In 5xFAD mice, the authors report that KED and EDR lessened dendritic-spine loss; KED 400 µg/kg daily from 2 to 4 months of age only tended to raise a neuroplasticity readout, with docking offered as a mechanistic hypothesis.

Editorial summary of a 2021 open-access original article in Pharmaceuticals (MDPI: doi:10.3390/ph14060515). Mouse and modeling work. A later publisher correction is PMID 39861198; this page cites the article. Public pages cite PubMed; the DOI is the OA record. Read the paper: PMID 34071923.

Methods

The authors used 5xFAD mice (B6SJL-Tg(APPSwFlLon, PSEN1M146LL286V)6799Vas/Mmjax). They report daily intraperitoneal KED at 400 µg/kg from 2 to 4 months of age when discussing neuroplasticity, and they examined dendritic-spine morphology in 5xFAD-M hippocampus after EDR or KED. Complementary work is in silico: docking of the tripeptides against dsDNA hexanucleotide libraries in B-form DNA, then mapping low-energy sites onto promoter regions of genes they associate with Alzheimer pathogenesis (including CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG). Protocol tables belong in the primary text; this page does not reprint them.

Findings

The authors report that KED and EDR prevented dendritic-spine loss in 5xFAD-M mice, and that KED “tended to increase neuroplasticity” on the in-vivo readout they used. Docking assigned EDR putative sites in promoters of apoptosis, cytoskeletal, antioxidant, and PPAR-related genes. They interpret spine preservation as an epigenetic-level neuroprotective effect of the two tripeptides in this amyloid model.

This is a single transgenic-mouse communication plus sequence modeling. Docking is not a binding assay. It is not a clinical trial and not a treatment claim for Alzheimer’s disease. Follow the PMID and the OA DOI.