Siena Biotech SpA, Strada del Petriccio e Belriguardo n°35, 53100 Siena, Italy.
FASEB J. 2011 Jun;25(6):1983-2000. doi: 10.1096/fj.10-163535. Epub 2011 Mar 10.
Humanin (HN) is a 24-residue peptide displaying a protective activity in vitro against a range of cytotoxic and neurotoxic insults, as well as mediating in vivo amelioration of Alzheimer disease (AD)-related memory impairment in experimental models. Published evidence suggests that the mechanisms through which HN exerts its cyto- and neuroprotective activity may include its secretion and binding to membrane-associated receptors. Here, we describe the identification of a new modulator of HN neuroprotective activity, V-set and transmembrane domain containing 2 like (VSTM2L), previously known as C20orf102. VSTM2L interacts with HN in both yeast and mammalian cells, is secreted in cultured cells, is present in serum, and is selectively expressed in the central nervous system. VSTM2L colocalizes with HN in distinct brain areas as well as in primary cultured neurons, where it plays a role in the modulation of neuronal viability. When tested in HN neuroprotection bioassays, VSTM2L acts as a strong antagonist of HN neuroprotective activity. In summary, VSTM2L is the first example of a secreted antagonist of HN and may play a role in the modulation of HN biological functions.
人源素 (HN) 是一种 24 个氨基酸组成的肽，具有体外抵抗多种细胞毒性和神经毒性损伤的保护活性，并能在实验模型中改善阿尔茨海默病 (AD) 相关的记忆障碍。已发表的证据表明，HN 发挥其细胞和神经保护活性的机制可能包括其分泌和与膜相关受体结合。在这里，我们描述了一种 HN 神经保护活性的新型调节剂的鉴定，即 V -set 和跨膜域包含 2 样 (VSTM2L)，以前称为 C20orf102。VSTM2L 在酵母和哺乳动物细胞中与 HN 相互作用，在培养细胞中分泌，存在于血清中，并在中枢神经系统中选择性表达。VSTM2L 与人源素在大脑的不同区域以及原代培养神经元中共定位，并在调节神经元活力方面发挥作用。当在 HN 神经保护生物测定中进行测试时，VSTM2L 作为 HN 神经保护活性的强拮抗剂发挥作用。总之，VSTM2L 是 HN 的第一个分泌拮抗剂的例子，可能在调节 HN 的生物学功能方面发挥作用。
