Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.

Traditionally considered to function solely as signaling molecules within the central nervous system (CNS), neurotransmitters are now recognized as key regulators of systemic homeostasis. They modulate interactions among the nervous, immune, and metabolic systems and influence the development of various diseases. This review systematically summarizes the fundamental properties of major neurotransmitters, including their biosynthesis, receptor subtypes, and key signaling pathways, and analyzes their context-dependent roles in cancer, neurodegenerative diseases (NDDs), and inflammatory disorders. A primary focus is the three-dimensional regulatory principle that determines their effects, namely: the receptor type they bind to, cellular microenvironment, and stage of the disease. These factors explain the bidirectional effects of neurotransmitters in disease. This review also evaluates current therapeutic approaches targeting neurotransmitter pathways, ranging from receptor-specific drugs to emerging combination therapies, and discusses challenges in clinical translation, such as off-target effects of nonspecific drugs and variable efficacy across disease types. By linking the fundamental mechanisms of neurotransmitter function to clinical challenges, this review provides a comprehensive framework for exploiting the neurotransmitter-immune axis to develop precise therapeutic strategies aimed at improving outcomes in cancer, NDDs, and inflammatory disorders.