The FK506-binding protein 5 (FKBP5) has been recently proposed as a drug target for treatment of stress-related disorders [1, 2]. FKBP5, a co-chaperone of the heat shock protein 90 (Hsp90), can decrease the affinity for glucocorticoids [3, 4] by binding through a tetratricopeptide repeat protein domain on the premature Hsp90—glucocorticoid receptors (GR) complex and change its conformation [4, 5]. FKBP5 also promotes the internalization of the immature GR complex, thus reducing the GR complex’s activity as a transcription factor [6, 7]. Glucocorticoids, released from the adrenals as a response to a stressor, exert their actions through GRs widespread in the HPA axis, mesocorticolimbic and striatal circuitries. Overlapping expression patterns of Fkbp5 with Nr3c1 (the gene coding for GR) throughout the rodent’s brain [8], and its ability as a negative regulator of GR, render FKBP5 a putative target of studies on stress [9] and addiction.
