In a pair of new papers, researchers at the University of California, San Diego School of Medicine and the Royal Netherlands Academy of Arts and Sciences upend a long-held view about the basic functioning of a key receptor molecule involved in signaling between neurons, and describe how a compound linked to Alzheimer's disease impacts that receptor and weakens synaptic connections between brain cells.
The findings are published in the Feb. 18 early edition of the Proceedings of the National Academy of Sciences.
Long the object of study, the NMDA receptor is located at neuronal synapses – the multitudinous junctions where brain cells trade electrical and chemical messages. In particular, NMDA receptors are ion channels activated by glutamate, a major "excitatory" neurotransmitter associated with cognition, learning and memory.
"NMDA receptors are well known to allow the passage of calcium ions into cells and thereby trigger biochemical signaling," said principal investigator Roberto Malinow, MD, PhD professor of neurosciences at UC San Diego School of Medicine.
The new research, however, indicates that NMDA receptors can also operate independent of calcium ions. "It turns upside down a view held for decades regarding how NMDA receptors function," said Malinow, who holds the Shiley-Marcos Endowed Chair in Alzheimer's Disease Research in Honor of Dr. Leon Thal (a renowned UC San Diego Alzheimer's disease researcher who died in a single-engine airplane crash in 2007).
Specifically, Malinow and colleagues found that glutamate binding to the NMDA receptor caused conformational changes in the receptor that ultimately resulted in a weakened synapse and impaired brain function.
They also found that beta amyloid – a peptide that comprises the neuron-killing plaques associated with Alzheimer's disease – causes the NMDA receptor to undergo conformational changes that also lead to the weakening of synapses.
"These new findings overturn commonly held views regarding synapses and potentially identify new targets in the treatment of Alzheimer's disease," said Malinow.
University of California - San Diego: http://www.ucsd.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Some, like dolphins or chimps, are sophisticated communicators. But do they have their own languages? Its a question that misses the point
Grey and harbour seals in the North Sea weave in and out of offshore wind farms in search of fish, which gather around turbines
Researchers have created wheat that is resistant to a common disease, using advanced gene editing methods.
An archaeological dig uncovers new clues about life and death in America's early history
Ted Stanley is giving $650 million to the Broad Institute of MIT and Harvard to find and treat the genetic underpinnings of mental illnesses. His son has bipolar disorder.
As far as agricultural genome research goes, this may be the best thing since sliced bread - wheat bread, that is.
The discovery and culturing of bacteria that eat and excrete electrons means we may soon find out just how little electricity fundamental life requires
The spectacularly well-preserved prehistoric sea creature sported compound eyes, body armor and two spiky claws for grabbing prey
The Beagle's library of more than 400 books has been reconstructed and made freely available in digital form
When the gorilla Willie B. had to move to a tiny cage at the Atlanta Zoo for six months, the vet staff decided to put Thorazine in the Coca-Cola he drank in the morning. Willie responded to the drug as many institutionalized humans do: He shuffled back and forth across his cage with dulled eyes.