With nearly 50 million dementia patients worldwide, Alzheimer’s disease is the most common neurodegenerative disease. Its main symptom is impairment of general cognitive abilities, including the ability to speak or remember.
The importance of finding a cure is widely understood as the population ages and life expectancy increases. However, even the cause of the grim disease has not yet been given a clear definition.
A research team from KAIST in the Department of Chemistry led by Professor Mi Hee Lim has taken the initiative to discover a new role for somatostatin, a protein-based neurotransmitter, in reducing the toxicity caused by the pathogenic mechanism that has been taken towards the development of Alzheimer’s disease.
The study was published in the July issue of nature chemistry Under “Conformational and functional alterations of the native somatostatin neuropeptide occur in the presence of copper and amyloid-beta”.
According to the amyloid hypothesis, abnormal deposition of Aβ proteins causes neuronal death. While Aβ clumps make up most of the old plaques through fibrosis, in recent studies, high concentrations of the transition metal have been found in plaques of Alzheimer’s patients.
This indicates a close interaction between metal ions and Aβ, which accelerates the fibrosis of proteins. Copper in particular is a redox-active transition metal that can produce large amounts of oxygen and cause dangerous oxidative stress on cell organelles.
Aβ proteins and transition metals can interact closely with neurotransmitters at synapses, but the direct effects of such abnormalities on the structure and function of neurotransmitters are not yet understood.
Professor Lim’s team discovered in their research that when somatostatin, a protein-based neurotransmitter, encounters the complexes of copper, Aβ, and metal Aβ, it self-assembles and ceases to perform its innate function of transmitting nerve signals, but begins to attenuate. Toxicity and clumping of Aβ metal complexes.
This research is by Dr. Jeon Han et al. From the Department of Chemistry KAIST, reported on the coordination structure between copper and somatostatin at the molecular level by which the agglomeration mechanism was proposed, and discovered the effects of somatostatin on the Aβ agglomeration pathway depending on the presence or absence of metals.
The team also confirmed somatostatin receptor binding, interactions with cell membranes, and effects on cytotoxicity for the first time to receive international attention.
Professor Mi Hee Lim said, “This research is of great importance in discovering a new role for neurotransmitters in the pathogenesis of Alzheimer’s disease.”
“We expect this research to contribute to the identification of the network of neurodegenerative diseases caused by aging, and to the development of biomarkers and medicine in the future,” she added.
This research was conducted jointly by Professor Seung-Hee Lee’s team from KAIST Department of Biological Sciences, Professor Kyung Park’s team from KAIST Department of Chemistry, and Professor Yulong Lee’s team from Peking University.
Financing: The research was funded by the Basic Science Research Program of the Korean National Research Foundation and KAIST.
About this research on Alzheimer’s disease news
author: yoonjo hong
Contact: Yoonju Hong – KAIST
picture: Photo credited to MetalloNeuroProteinoChemistry مركز
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“Conformational and functional alterations of the native neuropeptide semomatostatin occur in the presence of copper and amyloid-β” by Mi Hee Lim et al. nature chemistry
The conformational and functional changes of the native somatostatin neuropeptide occur in the presence of copper and amyloid-β
The development of neurodegenerative disorders can lead to impaired neurotransmission. However, the role of pathogens associated with these diseases and their influence on the structures and functions of neurotransmitters has not been clearly defined.
Here we report the finding that conformational and functional changes of a native neuropeptide, somatostatin (SST), occur in the presence of copper ions, metal-free amyloid-β (Aβ) and Aβ (metal-Aβ) found as pathogenic. Factors in the brains of Alzheimer’s patients.
These pathological elements induce SST self-assembly, thus preventing it from binding to the receptor. In the reverse direction, SST markedly modulates the assembly profiles of Aβ species in the presence of metal ions, attenuating their cytotoxicity and their interactions with cell membranes.
Our work demonstrates the loss of the normal function of the SST as a neurotransmitter and the gain of its modulatory function against Aβ metal under pathological conditions.