Dec 10, 2013

Deletion of calcineurin from astrocytes reproduces proteome signature of Alzheimer's disease and epilepsy and predisposes to seizures

BioRxiv : the Preprint Server for Biology
Joanna DembowyDmitry Lim

Abstract

Calcineurin (CaN), acting downstream of intracellular calcium signals, orchestrates cellular remodelling in many cellular types. In astrocytes, principal homeostatic cells in the central nervous system (CNS), CaN is involved in neuroinflammation and gliosis, while its role in healthy CNS or in early neuro-pathogenesis is poorly understood. Here we report that in mice with conditional deletion of CaN from GFAP-expressing astrocytes (astroglial calcineurin KO, ACN-KO), at 1 month of age, transcription was not changed, while proteome was deranged in hippocampus and cerebellum. Gene ontology analysis revealed overrepresentation of annotations related to myelin sheath, mitochondria, ribosome and cytoskeleton. Overrepresented pathways were related to protein synthesis, oxidative phosphorylation, mTOR and neurological disorders, including Alzheimer′s disease (AD) and seizure disorder. Comparison with published proteomics datasets shows significant overlap with the proteome of a familial AD mouse model and of human subjects with drug-resistant epilepsy. Strikingly, beginning from about 5 months of age ACN-KO mice develop spontaneous tonic-clonic seizures with inflammatory signature of epileptic brain. Altogether, our data suggest that ...Continue Reading

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Mentioned in this Paper

glycogen synthase kinase 3 beta
Biochemical Pathway
GSK3A
Adenosquamous Carcinoma
JUP gene
Transdifferentiation
Notch
Mammary Gland
Squamous Transitional Epithelial Cell Count
Mammary Gland Development

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