Research Papers:

Neuron-derived transthyretin modulates astrocytic glycolysis in hormone-independent manner

Alina Zawiślak, Piotr Jakimowicz, James A. McCubrey and Dariusz Rakus _

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Oncotarget. 2017; 8:106625-106638. https://doi.org/10.18632/oncotarget.22542

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Alina Zawiślak1, Piotr Jakimowicz2, James A. McCubrey3 and Dariusz Rakus1

1Department of Physiology and Molecular Neurobiology, Faculty of Biological Sciences, University of Wroclaw, Wroclaw, Poland

2Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland

3Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, Greenville, NC, USA

Correspondence to:

Dariusz Rakus, email: [email protected]

Keywords: astrocyte-neuron lactate shuttle; brain metabolism; cAMP/PKA signalling; GSK3; PI3K/AKT pathway

Received: August 23, 2017     Accepted: November 01, 2017     Published: November 20, 2017


It has been shown that neurons alter the expression of astrocytic metabolic enzymes by secretion of until now unknown molecule(s) into extracellular fluid. Here, we present evidence that neuron-derived transthyretin (TTR) stimulates expression of glycolytic enzymes in astrocytes which is reflected by an increased synthesis of ATP. The action of TTR is restricted to regulatory enzymes of glycolysis: phosphofructokinase P (PFKP) and pyruvate kinase M1/M2 isoforms (PKM1/2). The regulation of PFK and PKM expression by TTR is presumably specific for brain tissue and is independent of the role of TTR as a carrier protein for thyroxine and retinol. TTR induced expression of PKM and PFK is mediated by the cAMP/PKA-dependent pathway and is antagonized by the PI3K/Akt pathway. Our results provide the first experimental evidence for action of TTR as a neuron-derived energy metabolism activator in astrocytes and describe the mechanisms of its action. The data presented here suggest that TTR is involved in a mechanism in which neurons stimulate degradation of glycogen-derived glucosyl units without significant modulation of glucose uptake by glial cells.

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