Carro E, Trejo J L, Gomez-Isla T, LeRoith D, Torres-Aleman I
Laboratory of Neuroendocrinology, Cajal Institute, CSIC, Madrid, Spain.
Nat Med. 2002 Dec;8(12):1390-7. doi: 10.1038/nm1202-793. Epub 2002 Nov 4.
Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-beta (Abeta), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain Abeta levels are found at an early age in mutant mice with low circulating IGF-I, and Abeta burden can be reduced in aging rats by increasing serum IGF-I. This opposing relationship between serum IGF-I and brain Abeta levels reflects the ability of IGF-I to induce clearance of brain Abeta, probably by enhancing transport of Abeta carrier proteins such as albumin and transthyretin into the brain. This effect is antagonized by tumor necrosis factor-alpha, a pro-inflammatory cytokine putatively involved in dementia and aging. Because IGF-I treatment of mice overexpressing mutant amyloid markedly reduces their brain Abeta burden, we consider that circulating IGF-I is a physiological regulator of brain amyloid levels with therapeutic potential.
胰岛素样生长因子I（IGF-I）是一种具有神经保护作用的激素，其血清水平在衰老过程中会下降，而参与阿尔茨海默病发病机制的β淀粉样蛋白（Aβ）则会在大脑中积累。在循环IGF-I水平较低的突变小鼠中，幼年时大脑Aβ水平就很高，而通过提高血清IGF-I水平，可降低老年大鼠的Aβ负荷。血清IGF-I与大脑Aβ水平之间的这种相反关系反映出IGF-I可能通过增强Aβ载体蛋白（如白蛋白和转甲状腺素蛋白）向大脑的转运来诱导大脑Aβ清除的能力。肿瘤坏死因子-α可拮抗这种作用，肿瘤坏死因子-α是一种假定参与痴呆和衰老的促炎细胞因子。由于用IGF-I治疗过表达突变淀粉样蛋白的小鼠可显著降低其大脑Aβ负荷，因此我们认为循环IGF-I是大脑淀粉样蛋白水平的生理调节因子，具有治疗潜力。
