Neurotrophins in Peripheral Neuropathy: Exploring Pathophysiological Mechanisms and Emerging Therapeutic Opportunities

Neuropathies, which encompass a wide array of peripheral nervous system disorders, present significant challenges due to their varied causes, such as metabolic diseases, toxic exposures, and genetic mutations. This review article, focused on the critical role of neurotrophins in peripheral neuropathy, highlights the intricate balance of neurotrophins necessary for nerve health and the pathophysiological consequences when this balance is disturbed. Neurotrophins, including Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin- 3 (NT-3), and Neurotrophin-4 (NT-4), are essential for neuronal survival, axonal growth, and synaptic plasticity. Their signaling pathways are crucial for maintaining peripheral nervous system integrity, primarily via the Tropomyosin receptor kinase (Trk) receptors and the p75 neurotrophin receptor p75(NTR). Dysregulation of neurotrophins is implicated in various neuropathies, such as diabetic neuropathy and chemotherapy-induced peripheral neuropathy, leading to impaired nerve function and regeneration. Understanding neurotrophin signaling intricacies and their alterations in neuropathic conditions is crucial for identifying novel therapeutic targets. Recent advancements illuminate neurotrophins' potential as therapeutic agents, promising diseasemodifying treatments by promoting neuronal survival, enhancing axonal regeneration, and improving functional recovery post-nerve injury. However, translating these molecular insights into effective clinical applications faces challenges, including delivery methods, target specificity, and the instability of protein-based therapies.