Reduced nicotinamide adenine dinucleotide phosphate in redox balance and diseases: a friend or foe?

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...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2022-08, Vol.43 (8), p.1889-1904
Main Authors: Koju, Nirmala, Qin, Zheng-hong, Sheng, Rui
Format: Article
Language:English
Subjects:
Aging
Alzheimer's disease
Biomedical and Life Sciences
Biomedicine
Biosensors
Cardiovascular diseases
Cofactors
Diabetes mellitus
Energy Metabolism
Enzymes
Homeostasis
Humans
Immunology
Internal Medicine
Ischemia
Medical Microbiology
Movement disorders
NAD - metabolism
NADP
NADPH-diaphorase
Neurodegenerative diseases
Oxidation
Oxidation-Reduction
Parkinson's disease
Pharmacology/Toxicology
Phosphates
Redox properties
Review
Review Article
Vaccine
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Summary: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.
ISSN:1671-4083
1745-7254
DOI:10.1038/s41401-021-00838-7