Mandal Pravat K, Pettegrew Jay W, McKeag Dennish W, Mandal Ratna
Western Psychiatric Institute and Clinic Department of Psychiatry, University of Pittsburgh Medical School, 3811 O'Hara Street, PA 15213, USA.
Neurochem Res. 2006 Jul;31(7):883-90. doi: 10.1007/s11064-006-9092-0. Epub 2006 Jun 29.
Alzheimer's disease (AD) is a significant contributor to cognitive decline and is responsible for about half of the cases of dementia in later life. Although exact etiology of AD is not known, however, many risk factors for AD are identified. Anesthesia for elderly patients is considered as a risk factor in AD as they frequently experience deterioration in cognitive function with long exposure to anesthetics during surgery. Inhaled anesthetic agents remain the mainstay for patients undergoing major surgical operations. This study using multidimensional NMR spectroscopy provides the first direct evidence in vitro that inhaled anesthetic, halothane specifically interacts with Abeta40 and Abeta42 peptide. Halothane induces structural alternation of Abeta peptide from soluble monomeric alpha-helical form to oligomeric beta-sheet conformation, which may hasten the onset of AD. Abeta42 is more prone to oligomerization compared to Abeta40 in the presence of halothane. The molecular mechanism of halothane induced structural alternation of Abeta peptide is discussed.
阿尔茨海默病（AD）是导致认知衰退的一个重要因素，约占晚年痴呆病例的一半。虽然AD的确切病因尚不清楚，但已确定了许多AD的风险因素。老年患者的麻醉被认为是AD的一个风险因素，因为他们在手术期间长时间接触麻醉剂后经常出现认知功能恶化。吸入麻醉剂仍然是接受大型外科手术患者的主要麻醉方式。本研究使用多维核磁共振光谱法在体外首次提供了直接证据，证明吸入麻醉剂氟烷与β淀粉样蛋白40（Aβ40）和β淀粉样蛋白42（Aβ42）肽有特异性相互作用。氟烷诱导Aβ肽的结构从可溶性单体α螺旋形式转变为寡聚体β折叠构象，这可能会加速AD的发病。在氟烷存在的情况下，与Aβ40相比，Aβ42更容易发生寡聚化。本文讨论了氟烷诱导Aβ肽结构改变的分子机制。
