Shiraz University of Medical Sciences, Shiraz, Iran.
Nitric Oxide. 2023 May 1;134-135:23-37. doi: 10.1016/j.niox.2023.03.003. Epub 2023 Apr 3.
Nitric oxide (NO), an enzymatic product of nitric oxide synthase (NOS), has been associated with a variety of neurological diseases such as Alzheimer's disease (AD). NO has long been thought to contribute to neurotoxic insults caused by neuroinflammation in AD. This perception shifts as more attention is paid to the early stages before cognitive problems manifest. However, it has revealed a compensatory neuroprotective role for NO that protects synapses by increasing neuronal excitability. NO can positively affect neurons by inducing neuroplasticity, neuroprotection, and myelination, as well as having cytolytic activity to reduce inflammation. NO can also induce long-term potentiation (LTP), a process by which synaptic connections among neurons become more potent. Not to mention that such functions give rise to AD protection. Notably, it is unquestionably necessary to conduct more research to clarify NO pathways in neurodegenerative dementias because doing so could help us better understand their pathophysiology and develop more effective treatment options. All these findings bring us to the prevailing notion that NO can be used either as a therapeutic agent in patients afflicted with AD and other memory impairment disorders or as a contributor to the neurotoxic and aggressive factor in AD. In this review, after presenting a general background on AD and NO, various factors that have a pivotal role in both protecting and exacerbating AD and their correlation with NO will be elucidated. Following this, both the neuroprotective and neurotoxic effects of NO on neurons and glial cells among AD cases will be discussed in detail.
一氧化氮（NO）是一氧化氮合酶（NOS）的酶产物，与多种神经退行性疾病有关，如阿尔茨海默病（AD）。长期以来，人们一直认为 NO 会导致 AD 中神经炎症引起的神经毒性损伤。然而，随着人们越来越关注认知问题出现之前的早期阶段，这种观点发生了转变。然而，它揭示了 NO 的一种代偿性神经保护作用，通过增加神经元兴奋性来保护突触。NO 通过诱导神经可塑性、神经保护和髓鞘形成，以及具有细胞溶解活性以减少炎症，从而对神经元产生积极影响。NO 还可以诱导长时程增强（LTP），这是神经元之间突触连接变得更强的过程。更不用说这些功能会导致 AD 得到保护。值得注意的是，毫无疑问，需要进行更多的研究来阐明神经退行性痴呆症中的 NO 途径，因为这可以帮助我们更好地理解它们的病理生理学，并开发更有效的治疗选择。所有这些发现使我们普遍认为，NO 既可以作为 AD 患者和其他记忆障碍患者的治疗剂，也可以作为 AD 中神经毒性和侵袭性因素的贡献者。在这篇综述中，在介绍了 AD 和 NO 的一般背景之后，将阐明在 AD 中起关键作用的各种因素，以及它们与 NO 的相关性。之后，将详细讨论 AD 情况下 NO 对神经元和神经胶质细胞的神经保护和神经毒性作用。
