Striatal astrocyte μ-crystallin (Crym) loss contributes to early-stage Huntington’s disease pathophysiology

Ollivier, Matthias, Xia, Shengnan, Cankar, Neža, Qvist, Filippa Liliendahl, Pelaz, Sara G., Neupane, Chiranjivi, Casha, Vanessa H., Kawaguchi, Riki, Skotte, Niels Henning, Al-Dalahmah, Osama and Khakh, Baljit S. 2026. Striatal astrocyte μ-crystallin (Crym) loss contributes to early-stage Huntington’s disease pathophysiology. Neuron 10.1016/j.neuron.2026.08.027

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Abstract

A striatal astrocyte subpopulation expressing μ-crystallin (gene: Crym) regulates perseverative behaviors, but its role in disease is unclear. We found that astrocytic Crym and μ-crystallin protein expression levels are reduced in human Huntington’s disease (HD) tissue, cerebrospinal fluid, and HD mouse models. Selective astrocytic μ-crystallin restoration in a HD mouse model improved astrocyte and neuronal morphology, electrophysiology, gene expression, and early-stage compulsive and repetitive behaviors. Late-stage motor deficits remained mostly unchanged. Approximately 32% of the μ-crystallin rescued astrocytic genes overlapped with those dysregulated in human HD, indicating conserved molecular corrections. These results identify μ-crystallin-expressing astrocytes as modulators of HD pathophysiology and suggest that restoring μ-crystallin or targeting Crym-positive astrocytes could be beneficial in early disease stages.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Cell Press
ISSN:	0896-6273
Date of First Compliant Deposit:	19 October 2026
Date of Acceptance:	31 August 2026
Last Modified:	19 Oct 2026 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/190292

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