Modeling CLN3 Batten disease in astrocytes reveals dysfunctions in mitochondria, fatty acid metabolism and chromatin dynamics

ABSTRACT: CLN3 Batten disease is a severe pediatric neurodegenerative disorder caused by mutations in the CLN3 gene, most commonly a 1 kb deletion affecting exons 7 and 8. While research has focused on neuronal dysfunction, glial cells are increasingly recognized as key contributors to disease pathology. Among them, astrocytes, the most abundant glial cell type in the brain, are essential for neuron health and may play critical roles in disease progression. Here, we present the first iPSC-derived astrocyte model from a patient with the 1 kb deletion. Transcriptomic and proteomic analyses during astrocyte differentiation revealed significant disruptions in mitochondrial function, fatty acid metabolism, and oxidative stress, with minimal impact on lysosomal homeostasis. These findings prompt the hypothesis that mitochondrial dysfunction may precede lysosomal defects in CLN3-deficient astrocytes. Restoring mitochondrial health could improve brain metabolism, inflammation control, neurotransmitter regulation, and neuronal survival, highlighting mitochondria as promising therapeutic targets in CLN3 Batten disease.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hipsc Cell

SUBMITTER: Animesh Sharma  

LAB HEAD: Mirta Mittelstedt Leal de Sousa

PROVIDER: PXD064202 | Pride | 2026-06-08

REPOSITORIES: Pride