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Astrocytic PEN-2 Governs Cerebral Edema via Autophagic Control of AQP4 Homeostasis

GSE305336 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/31 Platform GPL24247
Summary
Cerebral edema, a life-threatening consequence of central nervous system (CNS) injury, lacks effective therapies. Aquaporin-4 (AQP4), the main water channel in astrocytes, plays critical roles in both the formation and resolution of edema, with unclear regulatory mechanisms. Here, we uncover a γ-secretase-independent function of presenilin enhancer 2 (Pen-2) in AQP4 turnover. Conditional Pen-2 inactivation in astrocytes results in metabolic alterations, severe cerebral edema and early lethality. Mechanistically, Pen-2 physically interacts with AQP4 to promote its degradation through the autophagy-lysosome pathway. Treatment with acetazolamide, an AQP4 inhibitor, reverses the edema phenotype in Pen-2-deficient mice, establishing AQP4 as a critical downstream effector. This study unveils a previously unrecognized Pen-2-AQP4 axis that governs brain water homeostasis and reveals a promising therapeutic target for edema treatment.
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Direct links to NCBI, no account and no request form: the whole study as GSE305336_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1305325 and SRA study SRP608672. Searching any of these in the dataset finder brings you back here.

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