TY  - JOUR
PY  - 2019//
TI  - Novel treatment targets based on insights in the etiology of depression: Role of IL-6 trans-signaling and stress-induced elevation of glutamate and ATP
JO  - Pharmaceuticals (Basel)
A1  - Kalkman, H.O.
SP  - 
EP  - 
VL  - 12
IS  - 3
N2  - Inflammation and psychological stress are risk factors for major depression and suicide. Both increase central glutamate levels and activate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Both factors also affect the function of the chloride transporters, Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2), and provoke interleukin-6 (IL-6) trans-signaling. This leads to measurable increases in circulating corticosteroids, catecholamines, anxiety, somatic and psychological symptoms, and a decline in cognitive functions. Recognition of the sequence of pathological events allows the prediction of novel targets for therapeutic intervention. Amongst others, these include blockade of the big-K potassium channel, blockade of the P2X4 channel, TYK2-kinase inhibition, noradrenaline α2B-receptor antagonism, nicotinic α7-receptor stimulation, and the Sgp130Fc antibody. A better understanding of downstream processes evoked by inflammation and stress also allows suggestions for tentatively better biomarkers (e.g., SERPINA3N, MARCKS, or13 C-tryptophan metabolism). © 2019 by the author. Licensee MDPI, Basel, Switzerland.<p /> <p>Language: en</p>
LA  - en
SN  - 1424-8247
UR  - http://dx.doi.org/10.3390/ph12030113
ID  - ref1
ER  -