A Korea Advanced Institute of Science and Technology (KAIST) research team has discovered that protein-based neurotransmitter, somatostatin, could play a new role in improving toxicity in Alzheimer’s occurring mechanism.
The study, led by Professor Lim Mi-hee of the Chemistry Department, was published in the July issue of Nature Chemistry, KAIST said on Monday.
There are nearly 50 million dementia patients worldwide, and Alzheimer’s is the most common neurodegenerative disease. Its typical symptom is impairment of thinking skills, such as verbal skills and memory. The need for treatment is increasing, but even its causes have yet to be known.
According to the amyloid hypothesis, the abnormal deposition of amyloid beta proteins leads to the extinction of nerve cells. An aggregation of amyloid beta possesses most of the elderly’s plaque through fibrosis, but recent studies revealed that plaques in Alzheimer’s disease patients are profound with high-density transition metals.
That indicates close interaction between a metal ion and amyloid beta. Metal ion accelerates fibrosis through the interaction with amyloid beta and copper. In addition, this oxidation-reduction active transfer metal produces a great amount of active oxygen, creating serious oxidation stress on cell organelles.
Amyloid beta proteins and transition metals can interact closely with neurotransmitters in synapses (neuro cellular junctions), but the direct effects of these pathological factors on the structure and signaling function of neurotransmitters have not yet been studied in detail.
The KAIST research team said that somatostatin, a protein-based neurotransmitter, goes under autoagglutination and loses its ability to transmit cell signals and instead controls the toxicity and cohesion of metallic amyloid.
The study revealed the coordination structure candidates of copper and somatostatin at the molecular level, proposed a coagulation mechanism, and identified the effect of somatostatin on the aggregation path of amyloid beta according to the presence or absence of metal. It is receiving global attention by proving the receptor binding of somatostatin, cell membrane interaction, and cytotoxicity changes for the first time in actual neuroblastoma.
Dr. Han Ji-yeon of KAIST’s Chemistry Department participated in the study as the lead author.
“The result of this research has profound significance in defining a new role of neurotransmitters within Alzheimer’s disease’s pathogenesis,” Professor Lim said. “We expect the research results to contribute to biomarker and treatment development in defining the pathogenic network of neurodegenerative disease due to aging.”