Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Universiteitsplein 1, B-2610 Antwerpen, Belgium.
Department of Neurology, Antwerp University Hospital, B-2650 Edegem, Belgium.
Int J Mol Sci. 2023 Feb 15;24(4):3866. doi: 10.3390/ijms24043866.
Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral sclerosis (ALS), are characterized by acute or chronic progressive loss of one or several neuronal subtypes. However, despite their increasing prevalence, little progress has been made in successfully treating these diseases. Research has recently focused on neurotrophic factors (NTFs) as potential regenerative therapy for neurodegenerative diseases. Here, we discuss the current state of knowledge, challenges, and future perspectives of NTFs with a direct regenerative effect in chronic inflammatory and degenerative disorders. Various systems for delivery of NTFs, such as stem and immune cells, viral vectors, and biomaterials, have been applied to deliver exogenous NTFs to the central nervous system, with promising results. The challenges that currently need to be overcome include the amount of NTFs delivered, the invasiveness of the delivery route, the blood-brain barrier permeability, and the occurrence of side effects. Nevertheless, it is important to continue research and develop standards for clinical applications. In addition to the use of single NTFs, the complexity of chronic inflammatory and degenerative diseases may require combination therapies targeting multiple pathways or other possibilities using smaller molecules, such as NTF mimetics, for effective treatment.
神经退行性疾病，包括阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）、多发性硬化症（MS）、脊髓损伤（SCI）和肌萎缩侧索硬化症（ALS），其特征是一种或多种神经元亚型的急性或慢性进行性丧失。然而，尽管这些疾病的患病率不断上升，但在成功治疗这些疾病方面几乎没有取得进展。最近的研究集中在神经营养因子（NTFs）作为神经退行性疾病潜在的再生治疗方法上。在这里，我们讨论了具有直接再生作用的 NTF 在慢性炎症和退行性疾病中的当前知识状态、挑战和未来展望。已经应用了各种 NTF 传递系统，如干细胞和免疫细胞、病毒载体和生物材料，将外源性 NTF 递送到中枢神经系统，取得了有希望的结果。目前需要克服的挑战包括传递的 NTF 数量、传递途径的侵袭性、血脑屏障通透性和副作用的发生。尽管如此，继续研究并为临床应用制定标准是很重要的。除了使用单一的 NTF 之外，慢性炎症和退行性疾病的复杂性可能需要针对多个途径的联合治疗，或者使用小分子（如 NTF 模拟物）等其他可能性进行有效治疗。
