# Neurotoxic amyloid β‐peptide and tau produce cytokine‐like effects on PMCA in glioblastoma cell lines, enhancing its activity and isoforms expression

## TL;DR

The study shows that amyloid β-peptide and tau, linked to Alzheimer's disease, cause astrocytes to become neurotoxic and increase calcium pump activity.

## Contribution

The novel finding is that Aβ and tau, like cytokines, induce PMCA upregulation in astrocytes, linking them to inflammation and cell damage.

## Key findings

- Aβ1-42 and tau increase PMCA activity and isoform expression in astrocytoma cells.
- These effects are similar to those caused by inflammatory cytokines.
- The transformation is associated with increased cell death and ROS generation.

## Abstract

The transformation of astrocytes into neurotoxic reactive astrocytes, classified as A1, by inflammatory cytokines, and their link to brain damage and neurodegenerative diseases has been widely documented. However, the roles of two biomarkers of Alzheimer's disease (AD), amyloid β‐peptide (Aβ) and tau, and that of calcium pumps which are involved in the fine‐tuning of calcium homeostasis, are poorly understood in astrocytes. In this study, we showed that treating astrocytoma U‐251 cells with a cocktail of cytokines significantly increased plasma membrane Ca2+‐ATPase (PMCA) activity and expression levels of the four PMCA isoforms. Moreover, treatment of cells with Aβ1‐42 or tau induced a similar upregulation of PMCA activity and isoform expression levels as cytokines. These effects support the close association of Aβ and tau with inflammation. This study may help better understand the role of PMCA in promoting calcium extrusion from astrocytes transformed by AD markers.

Two biomarkers of Alzheimer's disease, amyloid β‐peptide (Aβ) and tau, induce the transformation of U‐251 and other glioblastoma cell lines into neurotoxic A1‐like reactive astrocytes. This transformation is produced by cytokines and is followed by upregulation of PMCA activity and isoform expression, and is closely associated with inflammation, as revealed by increased cell death and ROS generation.