AANS Neurosurgeon | Volume 28, Number 4, 2019

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Taste-related Protein Provides Target for Drugs to Treat Neurological Disorders

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Understanding how the brain processes sweet, bitter and umami tastes may one day help researchers design more effective drugs for neurological disorders.

Van Andel Institute scientists have for the first time revealed the near atomic-level structure of a calcium homeostasis modulator (CALHM), a type of protein that plays critical roles in processing taste stimuli and mitigating toxicity in brain cells. These proteins work by sensing chemical and electrical changes in their environment — in the taste buds, for example — and relaying the information back to the brain.

They also help regulate calcium concentrations and amyloid-beta protein levels in the central nervous system. Previous research has shown that abnormal changes in CALHMs — and the resulting dysregulation of calcium or build-up of amyloid-beta — can contribute to Alzheimer’s disease, stroke and other neurological conditions.

“This is the first time we’ve been able to visualize one of these important proteins with such clarity. Until now, we didn’t know what they looked like or how they worked,” said Wei Lü, Ph.D., an assistant professor at VAI and co-corresponding author of the study. “Our molecular blueprint of calcium homeostasis modulator 2 lays the groundwork for understanding the broader family of CALHMs, which could inform therapeutic development down the road.”

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