# Hypergravity and ERK Inhibition Combined Synergistically Reduce Pathological Tau Phosphorylation in a Neurodegenerative Cell Model

**Authors:** Valerio Mignucci, Ivana Barravecchia, Davide De Luca, Giacomo Siano, Cristina Di Primio, Jack J. W. A. van Loon, Debora Angeloni

PMC · DOI: 10.3390/cells14141058 · 2025-07-10

## TL;DR

Hypergravity combined with ERK inhibition reduces harmful Tau protein changes in a lab model of neurodegeneration.

## Contribution

The synergistic effect of hypergravity and ERK inhibition on Tau phosphorylation is newly demonstrated in a neurodegenerative cell model.

## Key findings

- 50× g hypergravity combined with PD-0325901 reduced Tau aggregate area in HT22 cells.
- The treatment decreased phosphorylation at key Tau residues pS262 and pS396.
- Hypergravity may help reduce cytoskeletal damage caused by Tau aggregation.

## Abstract

This study evaluates the effects of hypergravity (HG) on a neurodegenerative model in vitro, looking at how HG influences Tau protein aggregation in Mouse Hippocampal Neuronal Cells (HT22) induced by neurofibrillary tangle seeds. Overall, 50× g significantly, synergistically, reduced the Tau aggregate Area when combined with ERK-inhibitor PD-0325901, correlating with decreased phosphorylation at critical residues pS262 and pS396. These findings suggest HG treatments may help mitigate cytoskeletal damage linked to Tau aggregation.

## Linked entities

- **Proteins:** MAPT (microtubule associated protein tau)
- **Chemicals:** PD-0325901 (PubChem CID 9826528)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}
- **Diseases:** Neurodegenerative (MESH:D019636)
- **Chemicals:** PD-0325901 (MESH:C506614)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** HT22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12293720/full.md

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Source: https://tomesphere.com/paper/PMC12293720