Law A, Gauthier S, Quirion R
Department of Neurology and Neurosurgery, McGill University, Montreal, H3B 2A1, Quebec, Canada.
Brain Res Brain Res Rev. 2001 Mar;35(1):73-96. doi: 10.1016/s0165-0173(00)00051-5.
Alzheimer's disease (AD) is the most common form of dementia, with progressive cognitive deficits being the primary symptom. AD is neuropathologically characterized by amyloid and neurofibrillary tangle depositions, basal forebrain cholinergic deficit, and extensive neuronal loss and synaptic changes in the cortex and hippocampus. Mutations of amyloid precursor protein or presenilin genes or apolipoprotein E gene polymorphism appear to affect amyloid formation, which in turn causes neuronal death via a number of possible mechanisms, including Ca(2+) homeostasis disruption, oxidative stress, excitotoxicity, energy depletion, neuro-inflammation and apoptosis. Nitric oxide (NO) is an enzymatic product of nitric oxide synthase, which exists in three isoforms. In addition to its vasoactive and immunological properties, NO has significant neurophysiological functions. However, NO can also be neurotoxic primarily due to its free radical properties, and it has been implicated in neurodegenerative diseases. Interestingly, there is increasing evidence that NO may have a role in the aforementioned AD pathogenetic mechanisms, and putative links between NO and AD are beginning to be recognized. This review focuses on these issues highlighting the possible relevance of NO in AD, either as a neuroprotective or neurotoxic agent.
阿尔茨海默病（AD）是最常见的痴呆形式，进行性认知缺陷是其主要症状。AD的神经病理学特征为淀粉样蛋白和神经原纤维缠结沉积、基底前脑胆碱能缺陷以及皮质和海马中广泛的神经元丢失和突触变化。淀粉样前体蛋白或早老素基因突变或载脂蛋白E基因多态性似乎会影响淀粉样蛋白的形成，进而通过多种可能机制导致神经元死亡，包括钙（Ca2+）稳态破坏、氧化应激、兴奋性毒性、能量耗竭、神经炎症和细胞凋亡。一氧化氮（NO）是一氧化氮合酶的酶促产物，一氧化氮合酶存在三种同工型。除了其血管活性和免疫特性外，NO还具有重要的神经生理功能。然而，NO也可能主要因其自由基特性而具有神经毒性，并且它与神经退行性疾病有关。有趣的是，越来越多的证据表明NO可能在上述AD发病机制中起作用，并且NO与AD之间的假定联系开始得到认可。本综述重点关注这些问题，强调NO在AD中作为神经保护剂或神经毒性剂的可能相关性。
