Samaddar Suman, Redhwan Moqbel Ali Moqbel, Eraiah Mohan Muttanahally, Koneri Raju
Research Institute, BGS Global Institute of Medical Sciences, Bengaluru, Karnataka, India.
Department of Pharmacology, KLE College of Pharmacy, Bengaluru, KLE Academy of Higher Education and Research, Belgavi, Karnataka, India.
CNS Neurol Disord Drug Targets. 2025;24(2):91-101. doi: 10.2174/0118715273327121240820074049.
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 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 disease-modifying 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.
神经病变涵盖了各种各样的周围神经系统疾病，由于其病因多样，如代谢疾病、接触毒素和基因突变，因而带来了重大挑战。这篇综述文章聚焦于神经营养因子在周围神经病变中的关键作用，强调了神经健康所需的神经营养因子的复杂平衡，以及这种平衡被打破时的病理生理后果。神经营养因子，包括神经生长因子（NGF）、脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）和神经营养因子-4（NT-4），对神经元存活、轴突生长和突触可塑性至关重要。它们的信号通路对于维持周围神经系统的完整性至关重要，主要涉及原肌球蛋白受体激酶（Trk）受体和p75神经营养因子受体p75（NTR）。神经营养因子的失调与各种神经病变有关，如糖尿病性神经病变和化疗引起的周围神经病变，导致神经功能受损和再生障碍。了解神经营养因子信号的复杂性及其在神经病变中的变化对于确定新的治疗靶点至关重要。最近的进展揭示了神经营养因子作为治疗药物的潜力，有望通过促进神经元存活、增强轴突再生和改善神经损伤后的功能恢复来实现疾病改善治疗。然而，将这些分子见解转化为有效的临床应用面临挑战，包括给药方法、靶点特异性以及基于蛋白质疗法的不稳定性。
