Scg3,也称为secretogranin III,是分泌粒蛋白家族中的一员,主要参与神经内分泌细胞的分泌粒形成和神经递质的储存与运输。Scg3在多种组织中广泛表达,包括神经、内分泌和免疫组织。近年来,研究表明Scg3在多种疾病的发生发展中发挥重要作用,包括眼科疾病、肿瘤、肥胖和代谢性疾病。
在眼科疾病方面,Scg3与脉络膜新生血管(CNV)的形成密切相关。CNV是老年性黄斑变性(nAMD)的病理特征之一,是发达国家老年人失明的主要原因。目前,CNV的治疗主要依赖于血管内皮生长因子(VEGF)抑制剂,如阿柏西普等,但治疗效果有限,且存在治疗抵抗和需要频繁眼内注射等问题。研究表明,Scg3可以诱导病理性血管生成,而不影响生理性血管生成。Scg3中和抗体可以选择性地抑制病理性血管生成,而不影响生理性血管生成。抗Scg3基因疗法可以有效地改善CNV,其疗效与抗VEGF基因疗法相当。因此,Scg3有望成为一种新的治疗CNV的药物靶点[1,2,5,6]。
在肿瘤方面,Scg3的表达与胶质瘤的恶性程度和临床预后相关。研究表明,Scg3蛋白表达与胶质瘤的恶性程度呈负相关,Scg3阳性表达的胶质母细胞瘤患者预后较好。此外,Scg3的基因多态性也与肥胖的发生相关。Scg3基因中的单核苷酸多态性(SNP)与肥胖表型显著相关,Scg3基因的变异可能通过调节下丘脑神经肽的分泌影响肥胖的发生[3,4,7]。
在代谢性疾病方面,Scg3与代谢功能障碍相关脂肪性肝病(MASLD)的发生发展相关。研究表明,Scg3是MASLD的候选治疗靶点之一,Scg3基因的变异与MASLD的发生风险相关[8]。
综上所述,Scg3是一种重要的分泌粒蛋白,参与多种生物学过程,包括神经递质的储存与运输、血管生成和肿瘤发生发展等。Scg3在多种疾病中发挥重要作用,包括眼科疾病、肿瘤、肥胖和代谢性疾病。Scg3有望成为一种新的治疗CNV、胶质瘤和MASLD的药物靶点。
参考文献:
1. Huang, Chengchi, Ji, Liyang, Kaur, Avinash, Webster, Keith A, Li, Wei. 2023. Anti-Scg3 Gene Therapy to Treat Choroidal Neovascularization in Mice. In Biomedicines, 11, . doi:10.3390/biomedicines11071910. https://pubmed.ncbi.nlm.nih.gov/37509549/
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