Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):315-9. doi: 10.1016/j.pnpbp.2010.07.032. Epub 2010 Aug 5.
Typically, cyclooxygenases (COXs) and 5-lipoxygenase (5-LOX), enzymes that generate biologically active lipid molecules termed eicosanoids, are considered inflammatory. Hence, their putative role in Alzheimer's disease (AD) has been explored in the framework of possible inflammatory mechanisms of AD pathobiology. More recent data indicate that these enzymes and the biologically active lipid molecules they generate could influence the functioning of the central nervous system and the pathobiology of neurodegenerative disorders such as AD via mechanisms different from classical inflammation. These mechanisms include the cell-specific localization of COXs and 5-LOX in the brain, the type of lipid molecules generated by the activity of these enzymes, the type and the localization of receptors selective for a type of lipid molecule, and the putative interactions of the COXs and 5-LOX pathways with intracellular components relevant for AD such as the gamma-secretase complex. Considering the importance of these multiple and not necessarily inflammatory mechanisms may help us delineate the exact nature of the involvement of the brain COXs and 5-LOX in AD and would reinvigorate the search for novel targets for AD therapy.
通常，环氧化酶（COXs）和 5-脂氧合酶（5-LOX）是生成生物活性脂质分子的酶，这些脂质分子被称为类二十烷酸，被认为是炎症的原因。因此，它们在阿尔茨海默病（AD）中的潜在作用在 AD 病理生物学的可能炎症机制框架内得到了探索。最近的数据表明，这些酶和它们生成的生物活性脂质分子可以通过不同于经典炎症的机制影响中枢神经系统的功能和神经退行性疾病（如 AD）的病理生物学。这些机制包括 COXs 和 5-LOX 在大脑中的细胞特异性定位、这些酶活性产生的脂质分子类型、对一种脂质分子有选择性的受体的类型和定位，以及 COXs 和 5-LOX 途径与与 AD 相关的细胞内成分（如 γ-分泌酶复合物）的潜在相互作用。考虑到这些多种且不一定是炎症的机制的重要性，可能有助于我们描绘大脑 COXs 和 5-LOX 参与 AD 的确切性质，并重新激发寻找 AD 治疗的新靶点的努力。
