Norata Davide, Capone Fioravante, Motolese Francesco, Marano Massimo, Rossi Mariagrazia, Calandrelli Rosalinda, Sacchetti Marta, Mantelli Flavio, Di Lazzaro Vincenzo, Pilato Fabio
Department of Medicine and Surgery, Unit of Neurology, Neurophysiology, Neurobiology and Psychiatry, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21 - 00128 Roma, Italy.
Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200 - 00128 Rome, Italy.
Aging Dis. 2024 Jul 15;16(4):2293-2314. doi: 10.14336/AD.2024.0573.
Rita Levi-Montalcini's 1953 discovery of nerve growth factor (NGF) in mouse sarcoma tumors marked a groundbreaking moment in neuroscience. NGF, a key signaling molecule, became the first identified neurotrophic factor, influencing the growth, differentiation, and survival of neurons in both peripheral and central nervous systems. NGF and related neurotrophic factors hold therapeutic potential for various neurological disorders, such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, amyotrophic lateral sclerosis, spinal cord injuries, neuropathies, traumatic brain injuries, and stroke. However, despite promising in vitro studies and animal models findings, NGF efficacy in patients remains unproven. Indeed, its use as a therapeutic agent faces challenges in delivery and clinical translation. This review delves into these challenges, exploring ongoing research on refined delivery methods, dosages, and safety profiles. Innovative strategies, including molecular mimicking, combination therapies, gene therapy, and coupling with neuromodulation techniques like transcranial magnetic stimulation and vagal nerve stimulation, are discussed. Incorporating nerve growth factor (NGF) into a comprehensive strategy may prove beneficial, particularly in non-neurodegenerative conditions such as stroke, trauma, and neuropathies. In these instances, NGF holds promise for promoting tissue regeneration and repair. Challenges persist in addressing the complexity of neurodegenerative pathologies for a combined therapeutic approach.
丽塔·列维-蒙塔尔奇尼1953年在小鼠肉瘤肿瘤中发现神经生长因子（NGF），这标志着神经科学领域的一个开创性时刻。NGF作为一种关键的信号分子，成为首个被鉴定出的神经营养因子，影响着外周和中枢神经系统中神经元的生长、分化和存活。NGF及相关神经营养因子对多种神经系统疾病具有治疗潜力，如阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症、脊髓损伤、神经病变、创伤性脑损伤和中风。然而，尽管体外研究和动物模型研究结果很有前景，但NGF在患者中的疗效仍未得到证实。事实上，将其用作治疗药物在给药和临床转化方面面临挑战。本综述深入探讨了这些挑战，探索了关于改进给药方法、剂量和安全性的 ongoing research。讨论了创新策略，包括分子模拟、联合疗法、基因疗法以及与经颅磁刺激和迷走神经刺激等神经调节技术相结合。将神经生长因子（NGF）纳入综合策略可能被证明是有益的，特别是在中风、创伤和神经病变等非神经退行性疾病中。在这些情况下，NGF有望促进组织再生和修复。在采用联合治疗方法应对神经退行性疾病的复杂性方面，挑战依然存在。
