Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences of Soochow University, Suzhou, 215123, China.
Acta Pharmacol Sin. 2022 Aug;43(8):1889-1904. doi: 10.1038/s41401-021-00838-7. Epub 2022 Jan 11.
The nicotinamide adenine dinucleotide (NAD/NADH) and nicotinamide adenine dinucleotide phosphate (NADP/NADPH) redox couples function as cofactors or/and substrates for numerous enzymes to retain cellular redox balance and energy metabolism. Thus, maintaining cellular NADH and NADPH balance is critical for sustaining cellular homeostasis. The sources of NADPH generation might determine its biological effects. Newly-recognized biosynthetic enzymes and genetically encoded biosensors help us better understand how cells maintain biosynthesis and distribution of compartmentalized NAD(H) and NADP(H) pools. It is essential but challenging to distinguish how cells sustain redox couple pools to perform their integral functions and escape redox stress. However, it is still obscure whether NADPH is detrimental or beneficial as either deficiency or excess in cellular NADPH levels disturbs cellular redox state and metabolic homeostasis leading to redox stress, energy stress, and eventually, to the disease state. Additional study of the pathways and regulatory mechanisms of NADPH generation in different compartments, and the means by which NADPH plays a role in various diseases, will provide innovative insights into its roles in human health and may find a value of NADPH for the treatment of certain diseases including aging, Alzheimer's disease, Parkinson's disease, cardiovascular diseases, ischemic stroke, diabetes, obesity, cancer, etc.
烟酰胺腺嘌呤二核苷酸（NAD/NADH）和烟酰胺腺嘌呤二核苷酸磷酸（NADP/NADPH）氧化还原对作为许多酶的辅助因子或/和底物，以维持细胞内氧化还原平衡和能量代谢。因此，维持细胞内 NADH 和 NADPH 平衡对于维持细胞内稳态至关重要。NADPH 生成的来源可能决定其生物学效应。新发现的生物合成酶和基因编码的生物传感器有助于我们更好地了解细胞如何维持区室化 NAD（H）和 NADP（H）池的生物合成和分布。区分细胞如何维持氧化还原偶联物池以发挥其整体功能并避免氧化还原应激是至关重要但具有挑战性的。然而，细胞内 NADPH 水平的缺乏或过量都会扰乱细胞的氧化还原状态和代谢稳态，导致氧化还原应激、能量应激，最终导致疾病状态，因此 NADPH 是有害的还是有益的仍然不清楚。对不同区室中 NADPH 生成的途径和调节机制的进一步研究，以及 NADPH 在各种疾病中发挥作用的方式，将为其在人类健康中的作用提供创新性的见解，并可能发现 NADPH 在治疗某些疾病（包括衰老、阿尔茨海默病、帕金森病、心血管疾病、缺血性中风、糖尿病、肥胖症、癌症等）方面的价值。
