Fig. 2: Derangement of HPA axis in pathological conditions.
From: α-synuclein in Parkinson’s disease: a central point of convergence with depression
Chronic psychological stress over-activates the HPA axis, resulting in hypercortisolemia. Under normal physiological conditions, HPA axis activation ends in the release of cortisol. Cortisol binds to glucocorticoid receptor (GR). GR translocates to the nucleus upon activation, modulating the transcription of genes associated with suppression of inflammation, cell survival and its own inhibitor FKBP5 (negative feedback to the HPA axis). Prolonged activation of HPA axis by chronic psychological stress ends in loss of GR and hypercortisolemia. Loss of GR leads to loss of neurotrophic support, neuroinflammation and HPA axis overactivity. Figure created in BioRender. Phansupkar, A. (2025) https://BioRender.com/qdvmv3k.
