A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice

Abstract

We investigated the effects of a heptapeptide, GPPGPAG, on memory improvement and neuritic regeneration in Alzheimer’s disease models to evaluate its potency as a new anti-Alzheimer’s disease (AD) therapy. The anti-AD effects of GPPGPAG were evaluated in Aβ-treated cortical neurons and 5XFAD, a mouse model of AD. Exposure of cortical neurons to Aβ25-35 for 3 days resulted in atrophy of axons and dendrites. Treatment with GPPGPAG improved the dendritic atrophy of Aβ-treated cortical neurons, but not axonal atrophy. Postsynaptic and presynaptic densities under Aβ1-42 exposure were increased by GPPGPAG post treatment. Oral administration of GPPGPAG to 5XFAD mice for 15 days improved significantly object recognition memory and dendritic density. Direct infusion of GPPGPAG into the lateral ventricle of 5XFAD mice for 28 days improved object recognition memory. Following oral administration of GPPGPAG in mice, the undigested heptapeptide was detected in the plasma and cerebral cortex. Analysis of target protein of GPPGPAG in neurons by DARTS method identified 14-3-3ε as a bound protein. The protective effect of GPPGPAG on Aβ1-42-induced dendritic atrophy was canceled by knockdown of 14-3-3ε. Taken together, these results suggest that GPPGPAG is orally available, transfers to the brain, and ameliorates memory dysfunction in AD brain, which is possibly mediated by 14-3-3ε-related dendritic restoration.

Supplementation of equine placenta extract on corneal wound in two dogs: Case report

“…However, it is unclear whether the results achieved in this study can be attributed solely to the nutritional role of the placental extract. Placental extracts contain bioactive peptides ( Yagi et al ., 1998 ; Togashi et al ., 2002 ; Tohda et al ., 2021 ). A representative example is JBP485, which promoted wound healing in the corneal epithelium and the secretion of tear fluid and mucin in the ocular surface epithelium in animal models ( Nagata et al ., 2015 ; Nakamura et al ., 2015 ).…”

Equine placental extract supplement as a night barking remedy in dogs with cognitive dysfunction syndrome

“…None of the active components in eqPE have yet been identified. However, at the basic research level, the active components of placental extract have been identified as heptapeptides, which have been shown to promote dendrite elongation and improve cognitive dysfunction in a mouse model of Alzheimer's disease (Tohda et al., 2021). Other studies have shown that hydroxyproline‐containing dipeptides identified from placental extracts efficiently promote mucin and tear fluid secretion in the rabbit ocular surface epithelium (Nakamura et al., 2015) and promote corneal epithelial cell growth, cell migration, and wound healing in the corneal epithelium (Nagata et al., 2015).…”

Experimental medicinal hepatitis. Hepatoprotective effects of the drug Laennec in models of toxic liver injury with paracetamol or alcohol

“…Масс-спектрометрическое de novo секвенирование «лёгкой» (до 1200 Да) пептидной фракции препарата позволило найти в составе ГПЧ пептиды LAGSGPAG (ингибитор тирозинкиназы BTK), VGPLGPLGPAG (ингибитор рецепторов андрогенов), DLGLPGAPGAP (ингибитор провоспалительной арахидон 5-липоксигеназы ALOX5) и GPSLGP (ингибитор провоспалительного воспаления NF-kB). Позднее было обнаружено, что весьма похожий по аминокислотному составу и структуре пептид GPPGPAG легко переносится через гематоэнцефалический барьер и улучшает дисфункцию памяти и атрофию дендритов у мышей с моделью болезни Альцгеймера [3].…”