Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA.
Pharmacol Rep. 2021 Apr;73(2):372-385. doi: 10.1007/s43440-020-00201-3. Epub 2021 Jan 2.
Granulocyte-colony stimulating factor (G-CSF), a member of the cytokine family of hematopoietic growth factors, is 19.6 kDa glycoprotein which is responsible for the proliferation, maturation, differentiation, and survival of neutrophilic granulocyte lineage. Apart from its proven clinical application to treat chemotherapy-associated neutropenia, recent pre-clinical studies have highlighted the neuroprotective roles of G-CSF i.e., mobilization of haemopoietic stem cells, anti-apoptotic, neuronal differentiation, angiogenesis and anti-inflammatory in animal models of neurological disorders. G-CSF is expressed by numerous cell types including neuronal, immune and endothelial cells. G-CSF is released in autocrine manner and binds to its receptor G-CSF-R which further activates numerous signaling transduction pathways including PI3K/AKT, JAK/STAT and MAP kinase, and thereby promote neuronal survival, proliferation, differentiation, mobilization of hematopoietic stem and progenitor cells. The expression of G-CSF receptors (G-CSF-R) in the different brain regions and their upregulation in response to neuronal insult indicates the autocrine protective signaling mechanism of G-CSF by inhibition of apoptosis, inflammation, and stimulation of neurogenesis. These observed neuroprotective effects of G-CSF makes it an attractive target to mitigate neurodegeneration associated with neurological disorders. The objective of the review is to highlight and summarize recent updates on G-CSF as a therapeutically versatile neuroprotective agent along with mechanisms of action as well as possible clinical applications in neurodegenerative disorders including AD, PD and HD.
粒细胞集落刺激因子（G-CSF）是细胞因子家族造血生长因子的成员，是一种 19.6 kDa 的糖蛋白，负责中性粒细胞谱系的增殖、成熟、分化和存活。除了其在治疗化疗相关中性粒细胞减少症方面的临床应用已得到证实外，最近的临床前研究还强调了 G-CSF 的神经保护作用，即在神经疾病动物模型中动员造血干细胞、抗细胞凋亡、神经元分化、血管生成和抗炎作用。G-CSF 由多种细胞类型表达，包括神经元、免疫细胞和内皮细胞。G-CSF 以自分泌方式释放，与 G-CSF-R 受体结合，进一步激活包括 PI3K/AKT、JAK/STAT 和 MAP 激酶在内的多种信号转导途径，从而促进神经元存活、增殖、分化和造血干细胞和祖细胞的动员。不同脑区 G-CSF 受体（G-CSF-R）的表达及其对神经元损伤的上调表明 G-CSF 通过抑制细胞凋亡、炎症和刺激神经发生来发挥自分泌保护信号机制。G-CSF 的这些观察到的神经保护作用使其成为减轻与神经退行性疾病相关的神经退行性变的有吸引力的治疗靶点。本综述的目的是强调和总结 G-CSF 作为一种治疗多功能神经保护剂的最新进展，以及其作用机制以及在包括 AD、PD 和 HD 在内的神经退行性疾病中的可能临床应用。
