BDNF–TRKB SIGNALLING AXIS: MOLECULAR MECHANISMS, NEUROTHERAPEUTIC INSIGHTS, AND THE EMERGING ROLE OF AKIBIA EQUINATA

Abstract

The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), constitute a critical neurotrophic axis that sustains neuronal survival, growth, and synaptic communication in the central nervous system (CNS). The dynamic interaction between BDNF and TrkB orchestrates complex intracellular signalling cascades—most notably the PI3K/Akt, MAPK/ERK, and PLC-γ pathways—that culminate in the activation of transcriptional regulators such as CREB and mTOR. These molecular routes underlie essential neural processes, including long-term potentiation (LTP), learning, memory, and stress resilience. However, genetic mutations, oxidative stress, neuroinflammation, and environmental stressors can impair this delicate signalling equilibrium, contributing to neurodegenerative and psychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, major depressive disorder, and stress-induced cognitive dysfunction.

Modern research has sought to therapeutically target the BDNF–TrkB pathway to restore neural homeostasis. Pharmacological agents such as 7,8-dihydroxyflavone (7,8-DHF) and LM22A-4 have shown potential as TrkB agonists, while non-pharmacological interventions—exercise, enriched environments, and dietary polyphenols—also enhance endogenous BDNF expression. Emerging among these modulators is Akibia equinata (syn. Akebia quinata), an East Asian medicinal vine whose extracts contain polyphenols and triterpene glycosides with neuroprotective potential. Experimental studies suggest that A. equinata enhances BDNF/TrkB–CREB signalling, upregulates antioxidant defences, and reverses stress-induced neuronal damage. This review comprehensively examines the BDNF–TrkB signalling network from molecular biology to therapeutic translation, emphasising Akibia equinata as a promising natural modulator for future neuroprotective drug development.