Biochemical Vulnerabilities of Monoamine Pathways: Cross-Kingdom Molecular Mimicry, Botanical Defense Mechanisms, and Synthetic Biosynthesis

The evolutionary conservation of monoamine neurotransmitters—including dopamine (), serotonin (), norepinephrine (), and the invertebrate analogue octopamine ()—presents one of the most fundamental and enduring biological paradoxes in neurophysiology.1 These foundational chemical messengers orchestrate a vast spectrum of physiological, homeostatic, and cognitive processes across virtually all domains of animal life.2 In both vertebrate and invertebrate taxa, monoaminergic systems regulate critical functions spanning motor control, reward-seeking behavior, nociception, temperature regulation, and complex sensory perception.2 Furthermore, recent neuroimmunological research indicates that monoamine signaling plays a pivotal role in modulating neuroinflammation by regulating proinflammatory cytokines and chemokines within the central nervous system (CNS), establishing a bidirectional interplay that significantly influences both neurodevelopment and the pathophysiology of neurodegenerative disorders.2 In addition to their classical roles as synaptic messengers, recent discoveries have revealed that monoamines such as dopamine and serotonin can directly attach to histone proteins (specifically H3) via the enzyme transglutaminase 2 (TG2), thereby acting as epigenetic regulators that modulate gene expression programs related to circadian rhythms and neural plasticity.