Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity.

ABSTRACT:

Background

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons (MNs). It was shown that human astrocytes with mutations in genes associated with ALS, like C9orf72 (C9) or SOD1, reduce survival of MNs. Astrocyte toxicity may be related to their dysfunction or the release of neurotoxic factors.

Methods

We used human induced pluripotent stem cell-derived astrocytes from ALS patients carrying C9orf72 mutations and non-affected donors. We utilized these cells to investigate astrocytic induced neuronal toxicity, changes in astrocyte transcription profile as well as changes in secretome profiles.

Findings

We report that C9-mutated astrocytes are toxic to MNs via soluble factors. The toxic effects of astrocytes are positiv

SUBMITTER: Birger A 

PROVIDER: S-EPMC6921360 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature