Molecular mechanism underlying stress response and adaptation.

Progress in brain research 2025

Yusuf JA, Akanbi ST, Olorunlowu DR, Opoola EK, Ogunlade EE, Kayode EA, Adejobi EO, Sulaiman YO, Odemakinde DI, Aworeni EO, Abdulmalik NI, Oluyemi DP, Isaac AE, Aromose OI, Adewale OM, Ogunrinde V, Adeleke TA, Adeleye OO

Abstract

Stress, a common life experience, impacts both mental and physical health, contributing to conditions such as anxiety and cardiovascular disease. It triggers physiological and psychological responses, primarily through the Hypothalamic-Pituitary-Adrenal (HPA) and Sympathetic-Adrenal-Medullary (SAM) axes, which are coordinated by the autonomic nervous system. Dysregulation of the glucocorticoid system, mediated by mineralocorticoid and glucocorticoid receptors, plays a critical role in neurodegenerative disorders like Alzheimer’s disease. Cellular pathways like PI3K/Akt, NF-κB, and AP-1 transcription factors maintain homeostasis during stress and are targets for therapeutic research. Epigenetic influences and genomic modifications highlight the long-lasting effects of stress on gene expression. Adaptive responses, such as allostasis, allow the body to maintain stability amid stress. However, excessive stress leads to allostatic load, negatively impacting the immune, endocrine, and nervous systems. Current treatments include pharmacological and lifestyle interventions, with emerging approaches such as psychobiotics and precision medicine offering future potential.

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