Scientists from the Washington University School of Medicine have
recently found something startling. Their recent article in the
Proceedings of the National Academy of Science explains that they’ve
found a protective protein, Nmnat1, that drastically reduces damage to
the brain when the brain is deprived of oxygen and blood flow. The
findings, which have so far only been done on mice, could potentially
create a new strategy for treating cerebral palsy, strokes,
Alzheimer’s, Parkinson’s Disease and other neurodegenerative diseases.

Five years ago, Jeff Milbrandt, MD, PhD first identified Nmnat1 when
he showed that the protein can protect against damage to peripheral
nerves in a person’s extremities. Another researcher, Phillip
Verghese, PhD, who was a postdoctoral researcher in Holtzman’s
laboratory, wanted to explore if the protein could also protect the
brain.

More recently, the researchers have looked at the effects of oxygen
and blood flow deprivation by comparing normal mice with those who
were genetically engineered to have higher-than-normal levels of
Nmnat1. What they found was shocking – and exciting. Within six
hours, the mice with the enhanced Nmnat1 showed less brain injury than
did those without. As they continued to follow up with the mice, they
found that the MRI scans of the brain showed that the Nmnat1 might be
even more protective than they had first imagined. The scans revealed
virtually no brain damage over time.

Hotzman explained that, “There are two types of injury in the
developing brain from inadequate oxygen and blood flow. One is
necrosis, where cells swell rapidly, burst and die; another is
apoptosis, where the cells shrink and die. We found that Nmnat1
prevents necrosis.”

While the researchers aren’t completely clear about how Nmnat1
protects the brain cells, they believe that it manages to block the
effects of the neurotransmitter glutamate, which overstimulates and
kills neighboring nerve cells.

As senior author David M. Holtzman, MD, the Andrew and Gretchen Jones
Professor and head of the Department of Neurology, explained, “Under
normal circumstances, the brain can handle a temporary disruption of
either oxygen or blood flow during birth, but when they occur together
and for long enough, long-term disability and death can result. If we
can use drugs to trigger the same protective pathway as Nmnat1, it may
be possible to prevent brain damage that occurs from these conditions
as well as from neurodegenerative diseases.”