Barrier Dysfunction as a Driver of Neuroendocrine Disorders: Inflammation, Autoimmunity, Stress Biology Crosstalk, and Therapeutic Opportunities
Samuel Oluwaseun Olojede, Babatunde Adebola Alabi, Sodiq Kolawole Lawal, Ayoola Isaac Jegede, Gladys Onyinye AdeoluwaBackground
Blood-brain, blood-hypothalamic, and blood-pituitary barriers are integral regulators of neuroendocrine homeostasis, and their dysfunction has been implicated in the pathogenesis of endocrine disorders, autoimmunity, neuroinflammation, and tumour biology through disruption of barrier integrity, immune surveillance, stress and neuroendocrine signalling. However, the integrated mechanisms through which dysfunction of these barriers drives neuroinflammation, endocrine autoimmunity, and stress-related pathophysiology, together with the therapeutic prospects of barrier restoration, remain poorly understood.
Purpose
Hence, the purpose of this review is to examine the roles of these barriers in maintaining neuroendocrine homeostasis, consequences of their dysfunction and therapeutic potentials of barrier restoration.
Major findings
This review shows key mechanisms by which aging, infection, trauma, and metabolic stress disrupt tight junction integrity and endothelial transport, causing neuroinflammation, hypothalamic-pituitary axis dysregulation, microglial activation, cytokine-mediated central nervous system entry, and enhanced autoantibody passage. It also emphasizes that these processes are involved in endocrine autoimmune diseases and influences neuroendocrine tumour progression through immune evasion and metastasis. Conclusion: In general, this review establishes that barrier dysfunction represents a central yet underexplored driver of neuroendocrine disease and emphasizes barrier restoration and immune modulation as promising strategy for precision-based therapeutic interventions.