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

Vladimir Khavinson,Nina Kolchina,Michael Petukhov,Nina Kraskovskaya,Anastasiia Ilina,Alexander Erofeev,Natalia Linkova,Ekaterina Mironova

doi:10.3390/ph14060515

Abstract

KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity in in vitro model of Alzheimer’s disease (AD). The objective of this paper was to study epigenetic mechanisms of EDR and KED peptides’ neuroprotective effects on neuroplasticity and dendritic spine morphology in an AD mouse model. Daily intraperitoneal administration of the KED peptide in 5xFAD mice from 2 to 4 months of age at a concentration of 400 μg/kg tended to increase neuroplasticity. KED and EDR peptides prevented dendritic spine loss in 5xFAD-M mice. Their action’s possible molecular mechanisms were investigated by molecular modeling and docking of peptides in dsDNA, containing all possible combinations of hexanucleotide sequences. Similar DNA sequences were found in the lowest-energy complexes of the studied peptides with DNA in the classical B-form. EDR peptide has binding sites in the promoter region of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG, GDX1 genes. Protein products of these genes are involved in AD pathogenesis. The neuroprotective effect of EDR and KED peptides in AD can be defined by their ability to prevent dendritic spine elimination and neuroplasticity impairments at the molecular epigenetic level.

Highlights

Alzheimer’s disease (AD) is a common neurodegenerative disease in the elderly and the most prevalent cause of dementia
To access dendritic spine morphology in vivo, we utilized the advantage of Mline mice, which expressed GFP in hippocampal neurons and generated the 5xFAD-M
Peptide KED provided the trend to normalization of LTP in 5xFAD mice

Summary

Introduction

Alzheimer’s disease (AD) is a common neurodegenerative disease in the elderly and the most prevalent cause of dementia. The prevalence of AD globally is increasing exponentially [2], and the number of people with dementia is predicted to increase to 131.5 million worldwide by. The most common form of AD is the late-onset AD (LOAD), defined as the AD with an onset at the age over 65, while the early-onset AD (EOAD) accounts for approximately 1% to 6% of all cases. The onset age of EOAD ranges roughly from 30 to. The disease is divided into sporadic cases (SAD) and familial cases (FAD). SAD results from a combination of genetic and environmental factors [4]. FAD is associated with mutations in one of the three genes: amyloid precursor protein (APP), presenilin 1 (PSEN1), presenilin 2 (PSEN2)

Objectives

Methods

Discussion

Conclusion