Novel enzyme pathway implicated in ALS

Written by Rhiannon Finnie

Researchers from the University of Missouri (MO, USA) have recently identified a potential therapeutic target for amyotrophic lateral sclerosis (ALS) that has the potential to lessen the severity and progression of the disease. Recently published in Cell Reports, the research reports this same enzyme pathway could also be target for recovery of patients who have suffered stroke and other neurological diseases.
Shinghua Ding, co-author of the study and associate professor of bioengineering and investigator in the Dalton Cardiovascular Research Center (MO, USA) explained:  “Our previous studies indicated that an enzyme known as nicotinamide phosphoribosyltransferase (NAMPT) is primarily expressed in the neurons in mouse models, and overexpression of NAMPT can protect against further brain injury following a stroke. For these reasons, NAMPT became a good target of study.”

Ding and his team observed that mice lacking the NAMPT enzyme resulted in progressive weight loss, hypothermia, motor neuron degeneration and motor function deficits. Nearly all of these symptoms are also observed in humans with ALS.

The team treated these mice with a molecule called nicotinamide mononucleotide (NMN), which acts as a substitute for the missing enzymatic product of NAMPT activity. Mice treated with the NMN molecule exhibited enhanced motor neuron function and overall improved health. Most importantly, the team demonstrated that NAMPT levels were significantly reduced in the spinal cord, indicating that NAMPT is involved in ALS pathogenesis.

Ding concluded: “What we’ve shown is that NAMPT is essential to neuronal function and viability. Remarkably, NMN improved health span, restored motor function and extended the lifespan in NAMPT-deficient mice. Based on our findings, it is an ideal candidate for further study, and the possible development of drugs in the diagnosis and treatment of ALS and stroke victims.”

Sources: Wang A, Zhang Q, Bao R et al. Deletion of Nampt in projection neurons of adult mice leads to motor dysfunction, neurodegeneration, and death. Cell Rep. (2017) (Epub ahead of print);