January 19, 2022

Shinghua Ding

Boosting the production of a certain metabolite in the human body may be key to preventing or treating debilitating diseases such as Parkinson’s and Lou Gehrig’s Disease. But more work is needed to determine how NAD⁺ and associated molecules respond differently in various areas of the brain and spinal cord. That’s one take-away from a new review paper Professor Shinghua Ding recently published in the journal Genes.

NAD⁺ stands for nicotinamide adenine dinucleotide. It’s a critical coenzyme found in every cell of the body and is involved in processes such as energy metabolism, cellular function and mitochondrial health. However, NAD⁺ levels decrease in many pathological conditions such as diseases in central nervous system, and as people age.

There is considerable evidence that shows NAD⁺ and precursor enzymes can treat ALS and Parkinson’s, as well as Huntington’s Disease and Charcot-Marie-Tooth Disease, Ding found.  He called for more investigation into how it could prove therapeutic for other motor neuron diseases.

Ding also suggests more study around the metabolites in the body that help production of NAD⁺.

Ding is Cramer W. LaPierre Professor of biomedical, biological and chemical engineering and an investigator at the Dalton Cardiovascular Research Center.

He was one of the first to connect NAD⁺ with the effects of brain injury in ischemic stroke and has continued to investigate how other enzymes boost NAD⁺ levels in neurons.

“Most people in biochemistry know NAD⁺ plays a very important role in cell metabolism and respiration and cell function,” Ding said. “But how NAD⁺ is synthesized is not talked about. More than twelve years ago, we started exploring how NAD affects cell functions and how metabolism and other functions are impaired when NAD⁺ levels are reduced.”

The paper is a continuation of his work on NAD⁺ and related enzymes, including a ground-breaking study in Cell Reports in 2017 that found NAD⁺ synthesis heavily relies on a metabolic enzyme known as NAMPT. In that study, they showed that removing NAMPT leads to motor dysfunction, impairs brain function, causes paralysis and can be fatal.

Last year, the team furthered the work and demonstrated that the deletion of NAMPT causes a decrease of NAD⁺ which leads to an increase of oxidative stress and neurodegeneration, direct causes of death. The 2021 paper, published in the Journal of Cerebral Blood Flow & Metabolism, used RNA sequence and metabolomic technologies to outline the effect of NAMPT on gene expression profile and metabolite content, identified important pathways and provided insight into the roles NAD plays in neurodegeneration. Research work in Dr. Ding’s lab has been supported by NIH and AHA for a number of years.