Leake A, Morris C M, Whateley J
MRC Neurochemical Pathology Unit, Institute for the Health of the Elderly, Newcastle General Hospital, Westgate Road, NE4 6BE, Newcastle upon Tyne, UK.
Neurosci Lett. 2000 Sep 22;291(3):201-3. doi: 10.1016/s0304-3940(00)01418-x.
Several lines of evidence indicate that there may be an inflammatory component to the pathology of Alzheimer's disease (AD), the major form of degenerative dementia in the elderly. Activity of inflammatory cells, and the elaboration of toxic molecules by such cells may be a significant factor in disease progression. In peripheral inflammatory states, the increased activity of matrix metalloproteinase (MMP) enzymes are a major cause of tissue breakdown and secondary damage in diseases such as rheumatoid arthritis. The activity of such enzymes in the normal or diseased central nervous system is, however, not well characterized. We have therefore determined the levels of MMP 1 (collagenase) in the normal human brain and in AD. MMP1 levels were relatively low though were significantly elevated by approximately 50% in AD in all cortical areas examined. Given the activity towards collagen of MMP1, it is possible that enhanced MMP1 activity in AD, may contribute to the blood-brain barrier dysfunction seen in AD.
多条证据表明,阿尔茨海默病(AD)——老年人退行性痴呆的主要形式——的病理过程中可能存在炎症成分。炎症细胞的活性以及此类细胞产生的毒性分子可能是疾病进展的一个重要因素。在周围炎症状态下,基质金属蛋白酶(MMP)酶活性增加是类风湿性关节炎等疾病中组织破坏和继发性损伤的主要原因。然而,此类酶在正常或患病中枢神经系统中的活性尚未得到充分表征。因此,我们测定了正常人类大脑和AD患者大脑中MMP 1(胶原酶)的水平。MMP1水平相对较低,但在所有检测的皮质区域中,AD患者的MMP1水平显著升高了约50%。鉴于MMP1对胶原蛋白的活性,AD中MMP1活性增强可能导致AD中出现的血脑屏障功能障碍。