Zia Bushra, Elmeky Mariam, Azimullah Sheikh, Jha Niraj Kumar, Nagoor Meeran Mohamed Fizur, Ojha Shreesh K
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, UAE.
School of Bioengineering & Biosciences, Lovely Professional University, Phagwara, 144411, Punjab, India.
Curr Neuropharmacol. 2025;23(10):1215-1231. doi: 10.2174/011570159X365720250225080257.
Neuroprotectin D1 (NPD1) has emerged as an integral lipid mediator with significant implications for maintaining neurological health. Being derived from docosahexaenoic acid (DHA), NPD1 is a specialized pro-resolving lipid mediator (SPM), consisting of a unique structure that attributes potent anti-inflammatory and neuroprotective properties crucial for maintaining nervous system homeostasis. It exerts its actions through diverse mechanisms, including the inhibition of proinflammatory cytokines, modulation of apoptosis, and promotion of cellular survival pathways. The dysregulation or deficiency of NPD1 has been implicated in the onset and progression of several neurodegenerative diseases, such as Alzheimer's, Parkinson's, and stroke, underscoring its critical role in maintaining neuronal health and disease prevention. Abnormal NPD1 signalling is associated with neuroinflammation, oxidative stress, and neuronal apoptosis, which in turn contribute significantly to the progression of neurological disorders. Understanding these pathways offers insights into potential therapeutic strategies aimed at targeting NPD1 to mitigate neurodegenerative processes and facilitate neural repair. The efforts in developing NPD1 analogs or mimetics are focused on enhancing endogenous NPD1 levels, attenuating neuroinflammation, and preserving neuronal integrity in disease contexts. This review provides a comprehensive exploration of NPD1, encompassing its structural characteristics, biochemical pathways, physiological roles, pathophysiological implications, and potential therapeutic applications in neurological disorders. Further, research into elucidating the precise mechanisms of NPD1 reveals that its clinical efficacy is crucial for harnessing its full potential as a therapeutic tool for neuroprotection and neural repair.
神经保护素D1（NPD1）已成为一种不可或缺的脂质介质，对维持神经健康具有重要意义。NPD1由二十二碳六烯酸（DHA）衍生而来，是一种特殊的促消退脂质介质（SPM），具有独特的结构，赋予其强大的抗炎和神经保护特性，这对维持神经系统的稳态至关重要。它通过多种机制发挥作用，包括抑制促炎细胞因子、调节细胞凋亡以及促进细胞存活途径。NPD1的失调或缺乏与多种神经退行性疾病的发生和发展有关，如阿尔茨海默病、帕金森病和中风，这突出了其在维持神经元健康和疾病预防中的关键作用。异常的NPD1信号传导与神经炎症、氧化应激和神经元凋亡相关，进而对神经疾病的进展有显著影响。了解这些途径有助于深入了解潜在的治疗策略，旨在靶向NPD1以减轻神经退行性过程并促进神经修复。开发NPD1类似物或模拟物的努力集中在提高内源性NPD1水平、减轻神经炎症以及在疾病情况下维持神经元完整性。本综述全面探讨了NPD1，包括其结构特征、生化途径、生理作用、病理生理意义以及在神经疾病中的潜在治疗应用。此外，对阐明NPD1精确机制的研究表明，其临床疗效对于充分发挥其作为神经保护和神经修复治疗工具的潜力至关重要。
