Isik Finula I, Thomson Shannon, Cueto John F, Spathos Jessica, Breit Samuel N, Tsai Vicky W W, Brown David A, Finney Caitlin A
Neuroinflammation Research Group, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Sydney, NSW, Australia.
St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Front Immunol. 2024 Dec 16;15:1514518. doi: 10.3389/fimmu.2024.1514518. eCollection 2024.
Neurodegeneration is characteristically multifaceted, with limited therapeutic options. One of the chief pathophysiological mechanisms driving these conditions is neuroinflammation, prompting increasing clinical interest in immunomodulatory agents. Growth differentiation factor 15 (GDF15; previously also called macrophage inhibitory cytokine-1 or MIC-1), an anti-inflammatory cytokine with established neurotrophic properties, has emerged as a promising therapeutic agent in recent decades. However, methodological challenges and the delayed identification of its specific receptor GFRAL have hindered research progress. This review systematically examines literature about GDF15 in neurodegenerative diseases and neurotrauma. The evidence collated in this review indicates that GDF15 expression is upregulated in response to neurodegenerative pathophysiology and increasing its levels in preclinical models typically improves outcomes. Key knowledge gaps are addressed for future investigations to foster a more comprehensive understanding of the neuroprotective effects elicited by GDF15.
神经退行性变具有多方面的特征，治疗选择有限。驱动这些病症的主要病理生理机制之一是神经炎症，这促使临床对免疫调节药物的兴趣日益增加。生长分化因子15（GDF15；以前也称为巨噬细胞抑制细胞因子-1或MIC-1）是一种具有既定神经营养特性的抗炎细胞因子，在近几十年已成为一种有前景的治疗药物。然而，方法学上的挑战以及其特异性受体GFRAL的延迟鉴定阻碍了研究进展。本综述系统地研究了有关GDF15在神经退行性疾病和神经创伤中的文献。本综述整理的证据表明，GDF15的表达在神经退行性病理生理反应中上调，并且在临床前模型中提高其水平通常会改善结果。针对未来的研究解决了关键的知识空白，以促进对GDF15引起的神经保护作用有更全面的理解。
