Physiological aspects of hormesis.

Hormesis-the adaptive response of cells and organisms to moderate, intermittent stress-has emerged as a promising framework for treating neurological and neuropsychiatric disorders. This biphasic dose-response phenomenon can benefit biological systems by inducing neural plasticity, improving cognitive function, and enhancing antioxidant and anti-inflammatory responses. Hormetic interventions including intermittent fasting, physical exercise, and environmental enrichment, among others, work through common molecular pathways. These approaches collectively modulate essential transcription factors such as NF-κB, CREB, and Nrf2, and consequent increases in the expression of neuroprotective genes, such as BDNF and heat shock proteins. The relationship between stress and biological outcomes follows an inverted U-shaped curve, where moderate stress triggers beneficial adaptations while chronic or excessive stress leads to allostatic load and pathology. This mechanistic understanding bridges traditional concepts of homeostasis with modern views on neuroplasticity and resilience. By elucidating the cellular and molecular mechanisms of hormetic responses, researchers can develop precisely calibrated, personalized interventions that may lead to therapeutic approaches to neurodegenerative conditions, neuropsychiatric disorders, and age-related cognitive decline.