Amity Institute of Biotechnology, Amity University, Lucknow, Uttar Pradesh, India

Stress is characterised as a condition of altered homeostasis, which might be due to psychological or physical factors. As humans face challenges, stress acts as an evolutionarily conserved adaptive reaction that helps organisms maintain homeostasis. However, several clinical illnesses, such as neuropsychiatric, metabolic, and neurodegenerative disorders, are caused by dysregulation of stress pathways. The continuity, severity and unpredictability of stress can produce numerous pathologies. The sympathetic-adrenomedullary (SAM) process and the hypothalamic-pituitary-adrenal (HPA) axis, which coordinate central and peripheral adaptations, are the key mediators of the stress response. A dynamic balance between pro-stress and anti-stress modulators, such as catecholamines, cytokines, reactive oxygen species, glucocorticoids, antioxidant systems, heat shock proteins, and transcriptional regulators like peroxisome proliferator-activated receptors, appears to control stress physiology. To comprehend the foundation of stress biology and to find novel biomarkers, it is essential to look at the insights of pro- and antistress modulators. The present review emphasizes the significance of their balance in defining physiological resistance vs disease susceptibility by offering a thorough insight into traditional and modern viewpoints on stress modulators. The understanding of these stress modulators helps researchers to identify specific stress biomarkers and plan treatment strategies, accordingly.