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

Suman Samaddar, Moqbel Ali Moqbel Redhwan, Mohan Muttanahally Eraiah, Raju Koneri
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Abstract

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.

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外周神经病变中的神经营养素:探索病理生理学机制和新的治疗机会》(Neurotrophins in Peripheral Neuropathy: Exploring Pathophysiological Mechanisms and Emerging Therapeutic Opportunities.
神经病变包括各种周围神经系统疾病,其病因多种多样,如代谢性疾病、毒性暴露和基因突变等,因此给人们带来了巨大的挑战。这篇综述文章重点论述了神经营养素在周围神经病变中的关键作用,强调了神经健康所必需的神经营养素之间错综复杂的平衡,以及这种平衡被打破时的病理生理后果。神经营养素,包括神经生长因子(NGF)、脑源神经营养因子(BDNF)、神经营养素-3(NT-3)和神经营养素-4(NT-4),对神经元的存活、轴突生长和突触可塑性至关重要。它们的信号通路对维持外周神经系统的完整性至关重要,主要是通过肌球蛋白受体激酶(Trk)受体和 p75 神经营养素受体 p75(NTR)。神经营养素失调与各种神经病变有关,如糖尿病神经病变和化疗引起的周围神经病变,从而导致神经功能和再生受损。了解神经营养素信号传导的复杂性及其在神经病变中的改变对于确定新的治疗靶点至关重要。最近的研究进展揭示了神经营养素作为治疗药物的潜力,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,神经营养素有望改变疾病的治疗方式。然而,将这些分子研究成果转化为有效的临床应用还面临着各种挑战,包括给药方法、靶点特异性以及基于蛋白质的疗法的不稳定性。
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