BUFFALO, N.Y. -- Only one drug is approved to treat persons with
mild to moderate Alzheimer's symptoms, despite the fact that the
brain protein at the core of this disease, the NMDA receptor, is
known to play a central role in several acute and chronic
neurodegenerative conditions that impair learning and memory.
Gabriela Popescu, Ph.D., assistant professor of biochemistry at
the University at Buffalo's School of Medicine and Biomedical
Sciences, is hoping to help change that situation.
She is beginning a new study, funded by the National Institutes
of Health, to investigate the mechanisms that control these
receptors, and to learn how to disrupt certain damaging NMDA
receptor functions, while leaving its other important functions
"Understanding how NMDA receptors work will help neuroscientists
address, rationally, neurodegenerative diseases such as
Alzheimer's, Parkinson's and Huntington's, and may provide novel
therapies for stroke and schizophrenia," said Popescu, a member of
the Neurodegenerative Group in the New York State Center of
Excellence in Bioinformatics and Life Sciences at UB.
"The shortage of useful therapies is particularly frustrating,
given the many distinct regulatory sites available on the NMDA
receptor. We are very hopeful we can address this urgent need for a
better understanding of how NMDA receptor activities are, or can
Her research is funded by a $1.6 million grant from the National
Institute of Neurological Disorders and Stroke.
The NMDA receptor and its neurotransmitter glutamate have been
the focus of intense neuroscience research in recent years.
"Ninety percent of all excitatory neuronal signaling in the
brain is controlled by glutamate, and half of it requires NMDA
receptors," Popescu said. "We need these proteins for the correct
wiring of our brains and throughout life to form and retain
memories, to learn new skills and behaviors. We cannot function
properly without them.
"Underactivity of NMDA receptors may be a cause of
schizophrenia, while overly active NMDA receptors kill neurons,
causing devastating brain damage following a stroke," she said.
"NMDA receptors also are involved with pernicious illnesses such as
Alzheimer's, Parkinson's and Huntington's in ways that are not yet
Popescu was lead researcher on a study, published in Nature in
2004, that described for the first time how these receptors can act
as "frequency discriminators," with the potential capacity to
determine whether a neuron will learn to become more or less
receptive to future experiences.
Her follow-up article in Molecular Pharmacology showed it should
be possible to find drugs that regulate certain NMDA receptor
functions, while leaving others alone.
"In addition to proving this important principle," said Popescu,
"we anticipate that the NIH project also will suggest novel
strategies, perhaps combinatorial, to control specifically the
receptor properties responsible for pathologic states, while
preserving its required functions in synaptic transmission and
"A better understanding of how these proteins work holds great
hope for addressing neurodegenerative diseases in the future."
The University at Buffalo is a premier research-intensive
public university, the largest and most comprehensive campus in the
State University of New York. The School of Medicine and Biomedical
Sciences is one of five schools that constitute UB's Academic