How a Neurotransmitter may be the Key in Controlling Alzheimer’s Toxicity​?

Researchers have uncovered a new role for somatostatin, a protein-based neurotransmitter, in lowering the toxicity caused in the pathogenic mechanism taken towards the development of Alzheimer’s disease. The study was published in the July issue of Nature Chemistry under the title, "Conformational and functional changes of the native neuropeptide somatostatin occur in the presence of copper and amyloid-β".

According to the amyloid hypothesis, the abnormal deposition of Aβ proteins causes the death of neuronal cells. While Aβ agglomerations make up most of the aged plaques through fibrosis, and in recent studies, high concentrations of transitional metal were found in the plaques from Alzheimer’s patients.

The Interplay of Neurotransmitter in Alzheimer’s Disease

This suggests a close interaction between metallic ions and Aβ, which accelerates the fibrosis of proteins. Copper in particular is a redox-activating transition metal that can produce large amounts of oxygen and cause serious oxidative stress on cell organelles. Aβ proteins and transition metals can closely interact with neurotransmitters at synapses, but the direct effects of such abnormalities on the structure and function of neurotransmitters are yet to be understood.

This research, by Dr. Jiyeon Han et al. from the KAIST Department of Chemistry, revealed the coordination structure between copper and somatostatin at a molecular level through which it suggested the agglomeration mechanism, and discovered the effects of somatostatin on Aβ agglomeration path depending on the presence or absence of metals. The team has further confirmed somatostatin’s receptor binding, interactions with cell membranes, and effects on cell toxicity for the first time to receive international attention.

Professor Mi Hee Lim said, "This research has great significance in having discovered a new role of neurotransmitters in the pathogenesis of Alzheimer’s disease." "We expect this research to contribute to defining the pathogenic network of neurodegenerative diseases caused by aging, and to the development of future biomarkers and medicine."

This research was conducted jointly by Professor Seung-Hee Lee’s team of KAIST Department of Biological Sciences, Professor Kiyoung Park’s Team of KAIST Department of Chemistry, and Professor Yulong Li’s team of Peking University.

The research was funded by Basic Science Research Program of the National Research Foundation of Korea and KAIST.

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Source-Eurekalert