Brain enzyme could prevent Alzheimer's, neurodegenerative disease

Researchers suggest the enzyme NMNAT2 may protect against cognitive decline.

June 3, 2016

An enzyme that protects the brain against oxidative stress may also protect against the formation of protein clumps - a hallmark of Alzheimer's, Parkinson's, and other neurodegenerative diseases.

This is the conclusion of a new study by researchers from Indiana University, who recently published their findings in the journal PLOS Biology.

The researchers believe their discovery could lead to the development of new drugs that preserve cognitive function.

An accumulation of protein clumps is known to occur in a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) - also known a Lou Gehrig's disease.

In Alzheimer's disease, for example, studies have shown that patients often experience a build-up of a protein called tau, which clumps together in nerve cells to form "tangles."

This process - known as proteinopathy - occurs with different proteins in a variety of brain diseases and is believed to play a role in their progression.

Now, study co-leader Yousuf Ali, of the Department of Psychological and Brain Sciences at Indiana, and colleagues have discovered an enzyme that might halt proteinopathy.Higher NMNAT2 levels linked to reduced cognitive decline

To reach their findings, the team analyzed the brains of more than 500 deceased elderly adults who were part of the Rush Memory and Aging Project before death. 

As part of the project, the cognitive function of each participant was assessed annually.

The researchers focused on levels of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). This is an enzyme known to produce a compound called nicotine adenine dinucleotide (NAD), which protects our brains against oxidative stress triggered by excess nerve cell activity.

From their analysis, the researchers found that adults who had higher levels of NMNAT2 in their brains were less likely to have experienced cognitive decline; individuals with lower levels of the enzyme were more likely to have had dementia.

This finding indicates that as well as protecting the brain against oxidative stress, NMNAT2 also protects the brain against memory and learning impairment.

Reduced tau in mice with higher NMNAT2 levels

Next, the team analyzed the brains of mice that had high levels of the tau protein.

The found that mice with higher levels of NMNAT2 in the hippocampus - the brain region important for learning and memory - had reduced levels of tau, compared with mice that had lower levels of NMNAT2.

Commenting on the possible implications of their findings, the authors say:

"Our work here suggests that NMNAT2 uses either its chaperone or enzymatic function to combat neuronal insults in a context-dependent manner. 

In Alzheimer disease brains, NMNAT2 levels are less than 50 percent of control levels, and we propose that enhancing NMNAT2 function may provide an effective therapeutic intervention to reserve cognitive function."

Overall, the researchers believe their finding could pave the way for new treatments for a number of neurodegenerative diseases.

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