Multifaceted role of nitric oxide in vascular dementia

Yang, Yi1; Ma, Kangrong1; Li, Shun2,*; Xiong, Tianqing1,2,3,*

Author Information

1Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China

2Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

3Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese and Western Medicine in Senile Diseases Control (Yangzhou University), Yangzhou, Jiangsu Province, China

*Correspondence to: Tianqing Xiong, PhD, 007418@yzu.edu.cn; Shun Li, MD, lis24@upmc.edu.

Funding:This work was supported by the China Postdoctoral Science Foundation, No. 2022M712689, and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China, No. 22KJB1800029, and Jiangsu Province Science and Technology Deputy Project Fund, No. FZ20240964 (all to TX).

Abstract

Vascular dementia is a highly heterogeneous neurodegenerative disorder induced by a variety of factors. Currently, there are no definitive treatments for the cognitive dysfunction associated with vascular dementia. However, early detection and preventive measures have proven effective in reducing the risk of onset and improving patient prognosis. Nitric oxide plays an integral role in various physiological and pathological processes within the central nervous system. In recent years, nitric oxide has been implicated in the regulation of synaptic plasticity and has emerged as a crucial factor in the pathophysiology of vascular dementia. At different stages of vascular dementia, nitric oxide levels and bioavailability undergo dynamic alterations, with a marked reduction in the later stages, which significantly contributes to the cognitive deficits associated with the disease. This review provides a comprehensive review of the emerging role of nitric oxide in the physiological and pathological processes underlying vascular dementia, focusing on its effects on synaptic dysfunction, neuroinflammation, oxidative stress, and blood‒brain barrier integrity. Furthermore, we suggest that targeting the nitric oxide soluble guanylate cyclase-cyclic guanosine monophosphate pathway through specific therapeutic strategies may offer a novel approach for treating vascular dementia, potentially improving both cognitive function and patient prognosis. The review contributes to a better understanding of the multifaceted role of nitric oxide in vascular dementia and to offering insights into future therapeutic interventions.

摘要

血管性痴呆是一种由多种因素诱发的高度异质性的神经退行性疾病。目前，对于血管性痴呆相关的认知功能障碍尚无明确的治疗方法。然而，早期发现和预防措施已被证明能有效降低发病风险并改善患者预后。一氧化氮在中枢神经系统的多种生理和病理过程中扮演着不可或缺的角色。近年来，研究发现一氧化氮参与调节突触可塑性，并已成为血管性痴呆病理生理过程中的关键因素。在血管性痴呆的不同阶段，一氧化氮水平及其生物利用度会发生动态变化，在疾病后期显著降低，这极大地加剧了与该病相关的认知缺陷。本综述全面阐述了一氧化氮在血管性痴呆生理和病理过程中新发现的作用，重点关注其对突触功能障碍、神经炎症、氧化应激和血脑屏障完整性的影响。此外，我们认为，通过特定的治疗策略靶向一氧化氮-可溶性鸟苷酸环化酶-环磷酸鸟苷通路，可能为治疗血管性痴呆提供一种新方法，有望改善认知功能和患者预后。本综述有助于更深入地理解一氧化氮在血管性痴呆中的多重作用，并为未来的治疗干预提供思路。