Exploring the Connection Between BDNF/TrkB and AC/cAMP/PKA/CREB Signaling Pathways: Potential for Neuroprotection and Therapeutic Targets for Neurological Disorders

Abstract

The BDNF/TrkB and AC/cAMP/PKA/CREB signaling pathways play a vital role in neuroplasticity, neuronal survival, and cognitive functions. This review explores its physiological and pathological implications in neurological disorders, with a focus on neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs). Neurological conditions increasingly burden public health, making understanding the biochemical mechanisms that underpin these diseases critical. BDNF, a neurotrophic factor, binds to the TrkB receptor, activating multiple intracellular signaling cascades that regulate cellular responses essential for neurogenesis, memory, and learning. Dysregulation within this pathway has been linked to various NDDs, as well as NPDs. Key components of the path, including adenylyl cyclase and cyclic AMP, mediate the effects of neurotransmitters and growth factors, influencing downstream targets like PKA and CREB, which are crucial for gene expression and synaptic changes. Furthermore, the review discusses the challenges of targeting this pathway for therapeutic interventions, including receptor isoform diversity, blood-brain barrier penetration, and potential side effects. Future strategies may include the development of selective TrkB modulators, nanoparticle carriers for drug delivery, and innovative gene therapy techniques. Advancing the understanding of this complex signaling network holds promise for effective interventions in treating neurological and psychiatric disorders, ultimately enhancing neuroprotection and cognitive resilience.

Keywords: AC; BDNF; CAMP; CREB; Cellular signaling; Neurological disorders; Neuroplasticity; PKA; Therapeutic strategies; TrkB.