Reduced Nicotinamide Adenine Dinucleotide Phosphate in Redox Balance and Diseases: a Friend or Foe?

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2022 Jan 12

PMID 35017669

Authors

Nirmala Koju

Zheng-Hong Qin

Rui Sheng

Affiliations

Soon will be listed here.

Abstract

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.

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