This open enrollment, choose a plan that includes access to our world-class providers. Get better care now

Menu
Search

Rewriting a Receptor’s Role

 

February 19, 2013  |  

Synaptic molecule works differently than thought; may mean new therapeutic targets for treating Alzheimer’s disease

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.

Co-authors on both papers are Helmut W. Kessels, Center for Neural Circuits and Behavior, Departments of Neuroscience and Biology, UCSD and Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences; and Sadegh Nabavi, Center for Neural Circuits and Behavior, Departments of Neuroscience and Biology, UC San Diego.

The research was funded in part by the National Institutes of Health (grants MH049159 and AG032132), the Shiley-Marcos Foundation, the Cure Alzheimer’s Foundation, and the Internationale Stichting Alzheimer Onderzoek.

# # #

Media Contact: Scott LaFee, 619-543-6163, slafee@ucsd.edu


Related Specialties

Memory Disorders Clinic



Media Contact

Share This Article


Related News

11/14/2019
Researchers identified non-coding regions of the human genome that control the development and function of four brain cell types and mapped genetic risk variants for psychiatric diseases. They found t ...
10/9/2019
Study finds when verbal memory test cut-offs were tailored to patient sex, more female patients and fewer male patients were considered to have amnesic mild cognitive impairment. This could change the ...
9/10/2019
UC San Diego researchers say that measuring how quickly a person’s pupil dilates while they are taking cognitive tests may be a low-cost, low-invasive method to aid in screening individuals at increas ...
7/23/2019
UC San Diego researchers have used the transcriptome — the sum of all messenger RNA (mRNA) molecules expressed from genes — to map protein-gene interactions involved in Alzheimer’s disease.



Follow Us