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Fatigue, including chronic and acute forms, is a prevalent and distressing symptom associated with a wide variety of diseases and physiological conditions, characterized by a decline in physical and/or mental performance and a subjective sense of tiredness[1][6]. While not a discrete molecular target, fatigue arises from complex interactions among genetic polymorphisms (notably in immune system genes such as TNF-α, IL-1β, IL-4, IL-6, and neurotransmitter-related genes), neurobiological pathways involving microglial activation and cytokine release in the brain, metabolic changes leading to accumulation of metabolites such as lactate and ammonia, oxidative stress resulting in protein and lipid peroxidation, and mitochondrial dysfunction[1][3][4][5][6][9]. Several measurable biomarkers of fatigue reflect metabolic and inflammatory changes, but no universal molecular marker or drugable target has been consistently identified. Fatigue is thus primarily a symptom or syndrome rather than a molecular entity amenable to traditional pharmacological targeting[4][5][7]. Key point: Fatigue is not itself a molecular or therapeutic target, but a symptom caused by dysfunction in multiple physiological, metabolic, immune, and neurobiological pathways[1][3][4][5][6][7][9].
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